PSA Level Less Than or Equal to Fifteen, PSA Level Less Than Ten, Stage IIA Prostate Cancer AJCC v7, Stage IIB Prostate Cancer AJCC v7, Stage II Prostate Cancer AJCC v7, Stage I Prostate Cancer AJCC v7
Conditions
Brief summary
This randomized phase II trial studies pomegranate-extract pill in preventing tumor growth in patients with prostate cancer that is limited to a certain part of the body (localized), who have chosen observation as their treatment plan. The use of pomegranate-extract pill may slow disease progression in patients with localized prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine the effect of pomegranate fruit extract (PFE) 1000 mg, taken daily for 1 year, on the plasma levels of insulin-like growth factor (IGF-1) from baseline to end of study (52 weeks) in participants undergoing active surveillance (AS) for early stage prostate cancer. SECONDARY OBJECTIVES: I. To assess compliance with a once daily oral administration of PFE versus placebo over a 52-week period of time. II. To assess the toxicity of PFE vs. placebo when taken daily for 52 weeks (+/- 1 week). III. To compare and correlate the effect of 52 weeks of daily dosing with PFE vs placebo on the end of study biopsy results including the presence or absence of tumor, the extent of tumor and Gleason scores. IV. To compare and correlate the modulation of the following biomarkers with response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core, tumor tissue from a positive core, and normal tissue adjacent to tumor from a positive core; plasma: insulin-like growth factor 1/IGF binding protein 3 ratio (IGF-1/IGFBP-3 ratio); prostate tissue (normal and abnormal): apoptosis (CASPASE 3), Ki-67, 8OHdG, IGF-1R, androgen receptor, IGF-1, IGFBP-3, prostate specific antigen (PSA). V. Measure PFE constituents/metabolites in plasma and urine for evidence of accumulation (trough levels): ellagic acid, dimethyl ellagic acid, dimethyl ellagic acid glucuronide (DMEAG), urolithin A, urolithin A-glucuronide, urolithin B and urolithin B-glucuronide. VI. Measure PSA doubling time (PSA DT) in serum, using the calculation provided on the Memorial Sloan Kettering Cancer Center website. VII. To assess the feasibility of cancer chemoprevention trials in a population of men undergoing active surveillance for prostate cancer. VIII. Measurement of serum testosterone. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive pomegranate-extract pill orally (PO) once daily (QD) for 52 weeks (+/- 1 week). GROUP II: Patients receive placebo PO QD for 52 weeks (+/- 1 week).
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
OTHERPlacebo
Given PO
DRUGPomegranate-Extract Pill
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have had a standard-of-care biopsy within 13 months of the baseline study visit and must have been diagnosed with low-grade, clinically localized prostate cancer (Gleason score =\< 3+3 with a PSA at baseline \< 10 ng/ml in participants \< 70 years of age, OR Gleason score =\< 3+4 with a PSA at baseline =\< 15 ng/ml in participants \>= 70 years of age); eligible participants will be those men who are able and willing to undergo AS with PSA monitoring and a scheduled biopsy performed at the end of the study * No concurrent treatment (hormonal, radiation or systemic chemotherapy) for prostate cancer during study enrollment is planned (unless participants demonstrate clinical evidence of prostate cancer progression such as symptoms, physical exam findings, a rapidly increasing PSA, or radiologic findings which confirm disease progression) * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 * White blood cells (WBC) \>= 3000/mm\^3 * Platelets \>= 100,000 mm\^3 * Hemoglobin \>= 10 g/dL * Total bilirubin =\< 1.5 x upper limit of institutional normal * Alkaline phosphatase =\< 1.5 x upper limit of institutional normal * Aspartate aminotransferase (AST) =\< 1.5 x upper limit of institutional normal * Alanine aminotransferase (ALT) =\< 1.5 x upper limit of institutional normal * Serum creatinine within 1.5 x upper limit of institutional normal * Sodium 135-144 mmol/L (inclusive) * Potassium 3.2-4.8 mmol/L (inclusive) * Participants will be required to use a medically-approved method of birth control or abstinence if their sexual partner is of child-bearing potential * Participants must be willing to forego foods, beverages and supplements containing pomegranate for the duration of the study * Ability to understand, and the willingness to sign, a written informed consent document
Exclusion criteria
* Any prior surgery to the prostate within 30 days of baseline procedures; NOTE: Biopsies are not considered surgeries * Evidence of other cancer(s) (excluding non-melanoma skin cancer) within last 5 years * Prior pelvic radiation for any reason * Participants cannot be taking 5-alpha-reductase inhibitors while on study or within 6 months of the baseline study visit * Participants may not be taking carbamazepine (tegretol) * Participants may not be receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PFE * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements * Any significant cardiac event(s) within the 12 months prior to registration, such as episode(s) of symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris or persistent, stable angina pectoris, or cardiac arrhythmia requiring medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma IGF-1 From Baseline to Post-Treatment | Baseline to 12 months | The primary endpoint for modulation of intermediate endpoint biomarkers will be the change in the plasma levels of IGF-1 by a quantitative assay (ELISA) from pre-study to post-treatment. The difference between these time points for the placebo group and the pomegranate fruit extract (PFE) group will be tested using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Up to 1 year | Patient toxicity throughout the study will be summarized in several ways; the presence or absence of any toxicity, worst CTCAE grade, and strongest investigator-defined relationship will all be examined and characterized by treatment arm, and analyzed appropriately (Wilcoxon rank-sum for ordinal data, Fisher's exact test for dichotomous data, and log rank test for time to event data). |
| Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Week 13, Week 26, Week 39, Week 52 | Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Week 13, Week 26, Week 39, Week 52 | Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Up to 1 year | — |
| Change in Serum Testosterone | up to 1 year | — |
| Prostate Specific Antigen Doubling Time (PSA DT) | up to 52 Weeks | PSA DT will be determined from PSA values obtained during study participation (baseline and weeks 13, 26, 39 and 52). The secondary endpoint of PSA DT is based on the value at study completion (week 52 or at point of early termination). However, PSA DT will be determined starting at week 26 (the earliest time point with 3 values) and week 39 and recorded. PSA doubling time is a measure based on the slope of the PSA at multiple time points. If the slope is relatively flat, the predicted doubling time could be far beyond the length of the actual study. As such, the value is not limited to the time frame over which data is collected from the participant. |
| Change in Tissue Biomarker Levels: PSA | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Tissue Biomarker Levels: IGF-1 | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Tissue Biomarker Levels: IGFBP-3 | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Compliance: Number of Participants Who Took Study Drug Per Protocol | Up to 1 year | Summarized by treatment arm with descriptive statistics, and tested for imbalance using Wilcoxon rank-sum test. Reported for each visit per protocol at Week 13, Week 26, Week 39, and Week 52 (end of study). |
| Change in Tissue Biomarker Levels: Ki-67 | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Tissue Biomarker Levels: IGF-Rb | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Tissue Biomarker Levels: 8OHdG | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Tissue Biomarker Levels: AR | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline at Week 13, Week 26, Week 39, and Week 52 | Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline at Week 13, Week 26, Week 39, and Week 52 | Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Change in Gleason Score | Baseline to 1 year | The Gleason Score is a grading system used to determine the aggressiveness of prostate cancer, scored 1-5 with 1 being healthy tissue and 5 being abnormal. Prostate cancers are assigned 2 scores to define the 2 most prevalent tissue types. They are added together (total range of 2-10). Typical scores fall between 6-10, the higher the overall score, the more likely the cancer will spread. |
| Change in Biopsy Tumor Involvement on Prostate Biopsy | Baseline to 1 year | Change in the length of biopsy cores that contained cancerous tissue from Baseline to end of study. |
| Change in Tissue Biomarker Levels: CASP3 | Baseline to Week 52 | Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
Countries
United States
Participant flow
Pre-assignment details
38 participants consented, only 30 eligible to start study
Participants by arm
| Arm | Count |
|---|---|
| Group I (Pomegranate-extract Pill) Patients receive pomegranate-extract pill PO QD for 52 weeks (+/- 1 week).
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Pomegranate-Extract Pill: Given PO | 14 |
| Group II (Placebo) Patients receive placebo PO QD for 52 weeks (+/- 1 week).
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO | 15 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group I (Pomegranate-extract Pill) | Group II (Placebo) | Total |
|---|---|---|---|
| Age, Customized Participant Age 18-64 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Customized Participant Age 65 years or older | 8 Participants | 7 Participants | 15 Participants |
| Body Mass Index | 29.15 kg/m^2 | 29.91 kg/m^2 | 29.55 kg/m^2 |
| Diastolic Blood Pressure | 81.64 mmHg | 83.60 mmHg | 82.66 mmHg |
| ECOG Performance Status ECOG 0 | 14 Participants | 15 Participants | 29 Participants |
| ECOG Performance Status ECOG 1 | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 14 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gleason Score 3+3=6 | 13 scores on a scale | 15 scores on a scale | 28 scores on a scale |
| Gleason Score 3+4=7 | 1 scores on a scale | 0 scores on a scale | 1 scores on a scale |
| Height | 174.73 cm | 177.23 cm | 176.02 cm |
| History or Baseline Presence of Disease / Abnormality Abdomen | 0 participants | 1 participants | 1 participants |
| History or Baseline Presence of Disease / Abnormality Genitalia | 0 participants | 1 participants | 1 participants |
| History or Baseline Presence of Disease / Abnormality Head/Eyes/Ears/Neck/Throat | 0 participants | 1 participants | 1 participants |
| History or Baseline Presence of Disease / Abnormality Neurological | 1 participants | 0 participants | 1 participants |
| History or Baseline Presence of Disease / Abnormality Prostate | 2 participants | 0 participants | 2 participants |
| History or Baseline Presence of Disease / Abnormality Skin | 1 participants | 2 participants | 3 participants |
| Pulse | 75.00 beats per minute | 68.13 beats per minute | 71.45 beats per minute |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 15 Participants | 28 Participants |
| Region of Enrollment United States | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 15 Participants | 29 Participants |
| Systolic Blood Pressure | 140.71 mmHg | 139.80 mmHg | 140.24 mmHg |
| Temperature | 97.81 degrees Fahrenheit | 97.62 degrees Fahrenheit | 97.71 degrees Fahrenheit |
| Weight | 88.92 kg | 94.53 kg | 91.82 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 15 |
| other Total, other adverse events | 14 / 14 | 13 / 15 |
| serious Total, serious adverse events | 2 / 14 | 2 / 15 |
Outcome results
Primary
Change in Plasma IGF-1 From Baseline to Post-Treatment
The primary endpoint for modulation of intermediate endpoint biomarkers will be the change in the plasma levels of IGF-1 by a quantitative assay (ELISA) from pre-study to post-treatment. The difference between these time points for the placebo group and the pomegranate fruit extract (PFE) group will be tested using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test.
Time frame: Baseline to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Plasma IGF-1 From Baseline to Post-Treatment | 19.12 ng/mL | Standard Deviation 21.22 |
| Group II (Placebo) | Change in Plasma IGF-1 From Baseline to Post-Treatment | 8.54 ng/mL | Standard Deviation 23.11 |
p-value: 0.19Wilcoxon rank-sum test
p-value: 0.211t-test, 2 sided
Secondary
Change in Biopsy Tumor Involvement on Prostate Biopsy
Change in the length of biopsy cores that contained cancerous tissue from Baseline to end of study.
Time frame: Baseline to 1 year
Population: One participant has a baseline measurement but does not have an end of study measurement, a change in the biopsy tumor involvement for this participant is therefore not possible to calculate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Biopsy Tumor Involvement on Prostate Biopsy | 0.34 mm | Standard Deviation 8.09 |
| Group II (Placebo) | Change in Biopsy Tumor Involvement on Prostate Biopsy | 1.88 mm | Standard Deviation 8.36 |
Comparison: Change in Tumor Volume from baseline to end of study per armp-value: 0.231Wilcoxon rank-sum test
Secondary
Change in Gleason Score
The Gleason Score is a grading system used to determine the aggressiveness of prostate cancer, scored 1-5 with 1 being healthy tissue and 5 being abnormal. Prostate cancers are assigned 2 scores to define the 2 most prevalent tissue types. They are added together (total range of 2-10). Typical scores fall between 6-10, the higher the overall score, the more likely the cancer will spread.
Time frame: Baseline to 1 year
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Gleason Score | Baseline | 0+0=0 | 0 Participants |
| Group I (Pomegranate-extract Pill) | Change in Gleason Score | Baseline | 3+3=6 | 13 Participants |
| Group I (Pomegranate-extract Pill) | Change in Gleason Score | Baseline | 3+4=7 | 1 Participants |
| Group I (Pomegranate-extract Pill) | Change in Gleason Score | Surgery Visit (52 Weeks) | 0+0=0 | 5 Participants |
| Group I (Pomegranate-extract Pill) | Change in Gleason Score | Surgery Visit (52 Weeks) | 3+3=6 | 7 Participants |
| Group I (Pomegranate-extract Pill) | Change in Gleason Score | Surgery Visit (52 Weeks) | 3+4=7 | 2 Participants |
| Group II (Placebo) | Change in Gleason Score | Surgery Visit (52 Weeks) | 3+3=6 | 8 Participants |
| Group II (Placebo) | Change in Gleason Score | Baseline | 0+0=0 | 0 Participants |
| Group II (Placebo) | Change in Gleason Score | Surgery Visit (52 Weeks) | 0+0=0 | 6 Participants |
| Group II (Placebo) | Change in Gleason Score | Baseline | 3+3=6 | 15 Participants |
| Group II (Placebo) | Change in Gleason Score | Surgery Visit (52 Weeks) | 3+4=7 | 1 Participants |
| Group II (Placebo) | Change in Gleason Score | Baseline | 3+4=7 | 0 Participants |
Secondary
Change in Levels of PFE Constituents/Metabolites: Urolithin B
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Change from Baseline at Week 13, Week 26, Week 39, and Week 52
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 13 | 0.00 ng | Standard Deviation 0 |
| Group I (Pomegranate-extract Pill) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 26 | 0.00 ng | Standard Deviation 0 |
| Group I (Pomegranate-extract Pill) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 39 | 709.24 ng | Standard Deviation 2653.74 |
| Group I (Pomegranate-extract Pill) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 52 | 1389.82 ng | Standard Deviation 4536.11 |
| Group II (Placebo) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 52 | 216.54 ng | Standard Deviation 838.66 |
| Group II (Placebo) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 13 | 0.00 ng | Standard Deviation 0 |
| Group II (Placebo) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 39 | 801.40 ng | Standard Deviation 2807.45 |
| Group II (Placebo) | Change in Levels of PFE Constituents/Metabolites: Urolithin B | Change from Baseline Week 26 | 156.86 ng | Standard Deviation 603.11 |
Comparison: Change from Baseline Week 13p-value: 1Wilcoxon rank-sum test
Comparison: Change from Baseline Week 26p-value: 0.18Wilcoxon rank-sum test
Comparison: Change from Baseline Week 39p-value: 0.62Wilcoxon rank-sum test
Comparison: Change from Baseline Week 52p-value: 0.536Wilcoxon rank-sum test
Secondary
Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Change from Baseline at Week 13, Week 26, Week 39, and Week 52
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 13 | 13491.88 ng | Standard Deviation 25612.57 |
| Group I (Pomegranate-extract Pill) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 26 | 29686.34 ng | Standard Deviation 38169.43 |
| Group I (Pomegranate-extract Pill) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 39 | 41322.95 ng | Standard Deviation 80948.44 |
| Group I (Pomegranate-extract Pill) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 52 | 21622.01 ng | Standard Deviation 29672.67 |
| Group II (Placebo) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 52 | -4882.23 ng | Standard Deviation 17075.55 |
| Group II (Placebo) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 13 | -8722.87 ng | Standard Deviation 32254.35 |
| Group II (Placebo) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 39 | -3688.76 ng | Standard Deviation 32749.71 |
| Group II (Placebo) | Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A | Change from Baseline Week 26 | -7119.63 ng | Standard Deviation 33532.58 |
Comparison: Change from Baseline Week 13p-value: 0.068Wilcoxon rank-sum test
Comparison: Change from Baseline Week 26p-value: 0.004Wilcoxon rank-sum test
Comparison: Change from Baseline Week 39p-value: 0.002Wilcoxon rank-sum test
Comparison: Change from Baseline Week 52p-value: <0.001Wilcoxon rank-sum test
Secondary
Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Week 13, Week 26, Week 39, Week 52
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 13 | 0.00 ratio | Standard Deviation 0.01 |
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 26 | 0.00 ratio | Standard Deviation 0.01 |
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 39 | 0.01 ratio | Standard Deviation 0.01 |
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 52 | 0.01 ratio | Standard Deviation 0.01 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 52 | 0.00 ratio | Standard Deviation 0.01 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 13 | 0.01 ratio | Standard Deviation 0.01 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 39 | -0.00 ratio | Standard Deviation 0.01 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3 | Change Baseline to Week 26 | -0.00 ratio | Standard Deviation 0.01 |
Comparison: Baseline to Week 13 p-valuep-value: 0.743Wilcoxon rank-sum test
Comparison: Baseline to Week 26 p-valuep-value: 0.305Wilcoxon rank-sum test
Comparison: Baseline to Week 39 p-valuep-value: 0.111Wilcoxon rank-sum test
Comparison: Baseline to Week 52 p-valuep-value: 0.395Wilcoxon rank-sum test
Secondary
Change in Plasma Biomarker Levels From Baseline: IGFBP-3
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Week 13, Week 26, Week 39, Week 52
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 13 | -102.91 ng/mL | Standard Deviation 501.07 |
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 26 | 10.55 ng/mL | Standard Deviation 560.69 |
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 39 | -309.11 ng/mL | Standard Deviation 455.91 |
| Group I (Pomegranate-extract Pill) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 52 | -137.67 ng/mL | Standard Deviation 363.48 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 52 | -0.39 ng/mL | Standard Deviation 498.02 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 13 | -195.57 ng/mL | Standard Deviation 592.17 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 39 | 89.34 ng/mL | Standard Deviation 381.47 |
| Group II (Placebo) | Change in Plasma Biomarker Levels From Baseline: IGFBP-3 | Change Baseline to Week 26 | 99.74 ng/mL | Standard Deviation 652.11 |
Comparison: Baseline to Week 13 p-valuep-value: 0.948Wilcoxon rank-sum test
Comparison: Baseline to Week 26 p-valuep-value: 0.711Wilcoxon rank-sum test
Comparison: Baseline to Week 39 p-valuep-value: 0.038Wilcoxon rank-sum test
Comparison: Baseline to Week 52 p-valuep-value: 0.445Wilcoxon rank-sum test
Secondary
Change in Serum Testosterone
Time frame: up to 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Serum Testosterone | Baseline | 9.37 pg/ml | Standard Deviation 5.23 |
| Group I (Pomegranate-extract Pill) | Change in Serum Testosterone | Week 26 | 11.43 pg/ml | Standard Deviation 10.48 |
| Group I (Pomegranate-extract Pill) | Change in Serum Testosterone | Week 52 | 14.83 pg/ml | Standard Deviation 19.84 |
| Group II (Placebo) | Change in Serum Testosterone | Baseline | 9.73 pg/ml | Standard Deviation 3.03 |
| Group II (Placebo) | Change in Serum Testosterone | Week 26 | 12.61 pg/ml | Standard Deviation 13.46 |
| Group II (Placebo) | Change in Serum Testosterone | Week 52 | 9.27 pg/ml | Standard Deviation 3.42 |
Comparison: Comparison of both arms at baselinep-value: 0.556Wilcoxon rank-sum test
Comparison: comparison of both arms at Week 26p-value: 0.647Wilcoxon rank-sum test
Comparison: comparison of both arms at end of study, week 52p-value: 0.948Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: 8OHdG
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Nuc Adjacent | -0.09 normalized optical density | Standard Deviation 0.13 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cyt Tumor | -0.58 normalized optical density | Standard Deviation 0.33 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cyt Benign | -0.15 normalized optical density | Standard Deviation 0.47 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cell Benign | -0.17 normalized optical density | Standard Deviation 0.43 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Nuc Tumor | -0.15 normalized optical density | Standard Deviation 0.08 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cell Adjacent | -0.31 normalized optical density | Standard Deviation 0.43 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cyt Adjacent | -0.28 normalized optical density | Standard Deviation 0.45 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cell Tumor | -0.50 normalized optical density | Standard Deviation 0.28 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Nuc Benign | -0.05 normalized optical density | Standard Deviation 0.15 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cell Tumor | 0.19 normalized optical density | Standard Deviation 0.47 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Nuc Benign | -0.02 normalized optical density | Standard Deviation 0.15 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Nuc Adjacent | 0.07 normalized optical density | Standard Deviation 0.16 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Nuc Tumor | 0.07 normalized optical density | Standard Deviation 0.2 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cyt Benign | 0.21 normalized optical density | Standard Deviation 0.54 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cyt Adjacent | 0.47 normalized optical density | Standard Deviation 0.54 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cyt Tumor | 0.41 normalized optical density | Standard Deviation 0.52 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cell Benign | 0.09 normalized optical density | Standard Deviation 0.39 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: 8OHdG | Change From Baseline: Cell Adjacent | 0.20 normalized optical density | Standard Deviation 0.4 |
Comparison: Change From Baseline: Nuc Benign p-valuep-value: 0.625Wilcoxon rank-sum test
Comparison: Change From Baseline: Nuc Adjacent p-valuep-value: 0.128Wilcoxon rank-sum test
Comparison: Change From Baseline: Nuc Tumor p-valuep-value: 0.045Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Benign p-valuep-value: 0.105Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Adjacent p-valuep-value: 0.066Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Tumor p-valuep-value: 0.005Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Benign p-valuep-value: 0.129Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Adjacent p-valuep-value: 0.066Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Tumor p-valuep-value: 0.013Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: AR
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: AR | Change From Baseline: Benign | 0.48 normalized optical density | Standard Deviation 1.07 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: AR | Change From Baseline: Adjacent | -0.38 normalized optical density | Standard Deviation 0.6 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: AR | Change From Baseline: Tumor | -1.22 normalized optical density | Standard Deviation 1.15 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: AR | Change From Baseline: Benign | -0.55 normalized optical density | Standard Deviation 1.87 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: AR | Change From Baseline: Adjacent | 1.02 normalized optical density | Standard Deviation 0.9 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: AR | Change From Baseline: Tumor | 0.38 normalized optical density | Standard Deviation 0.94 |
Comparison: Change from Baseline: Benign p-valuep-value: 0.143Wilcoxon rank-sum test
Comparison: Change from Baseline: Adjacent p-valuep-value: 0.037Wilcoxon rank-sum test
Comparison: Change from Baseline: Tumor p-valuep-value: 0.111Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: CASP3
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Nuc Adjacent | -0.40 normalized optical density | Standard Deviation 1.06 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cyt Tumor | -0.45 normalized optical density | Standard Deviation 1.66 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cyt Benign | -0.49 normalized optical density | Standard Deviation 1.43 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cell Benign | -0.54 normalized optical density | Standard Deviation 1.52 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Nuc Tumor | -0.34 normalized optical density | Standard Deviation 1.06 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cell Adjacent | -0.40 normalized optical density | Standard Deviation 1.16 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cyt Adjacent | -0.42 normalized optical density | Standard Deviation 1.31 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cell Tumor | -0.35 normalized optical density | Standard Deviation 1.35 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Nuc Benign | -0.61 normalized optical density | Standard Deviation 1.74 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cell Tumor | 0.01 normalized optical density | Standard Deviation 0.36 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Nuc Benign | 0.57 normalized optical density | Standard Deviation 1.74 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Nuc Adjacent | 0.38 normalized optical density | Standard Deviation 1.55 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Nuc Tumor | 0.04 normalized optical density | Standard Deviation 0.43 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cyt Benign | -0.01 normalized optical density | Standard Deviation 1.3 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cyt Adjacent | 0.54 normalized optical density | Standard Deviation 1.44 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cyt Tumor | -0.00 normalized optical density | Standard Deviation 0.33 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cell Benign | 0.23 normalized optical density | Standard Deviation 1.4 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: CASP3 | Change From Baseline: Cell Adjacent | 0.43 normalized optical density | Standard Deviation 1.42 |
Comparison: Change From Baseline: Nuc Benign p-valuep-value: 0.167Wilcoxon rank-sum test
Comparison: Change From Baseline: Nuc Adjacent p-valuep-value: 0.391Wilcoxon rank-sum test
Comparison: Change From Baseline: Nuc Tumor p-valuep-value: 0.713Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Benign p-valuep-value: 0.452Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Adjacent p-valuep-value: 0.391Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Tumor p-valuep-value: 0.713Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Benign p-valuep-value: 0.344Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Adjacent p-valuep-value: 0.391Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Tumor p-valuep-value: 0.713Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: IGF-1
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Nuc Adjacent | -0.58 normalized optical density | Standard Deviation 2.78 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cyt Tumor | -0.65 normalized optical density | Standard Deviation 1.64 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cyt Benign | -0.43 normalized optical density | Standard Deviation 1.35 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cell Benign | -0.29 normalized optical density | Standard Deviation 1.45 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Nuc Tumor | -0.53 normalized optical density | Standard Deviation 2.39 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cell Adjacent | -0.53 normalized optical density | Standard Deviation 2.17 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cyt Adjacent | -0.52 normalized optical density | Standard Deviation 1.77 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cell Tumor | -0.61 normalized optical density | Standard Deviation 1.99 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Nuc Benign | -0.10 normalized optical density | Standard Deviation 1.65 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cell Tumor | 1.06 normalized optical density | Standard Deviation 1.02 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Nuc Benign | 0.57 normalized optical density | Standard Deviation 1.91 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Nuc Adjacent | 1.74 normalized optical density | Standard Deviation 1.45 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Nuc Tumor | 1.06 normalized optical density | Standard Deviation 1.41 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cyt Benign | 0.21 normalized optical density | Standard Deviation 1.38 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cyt Adjacent | 1.47 normalized optical density | Standard Deviation 1.15 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cyt Tumor | 1.10 normalized optical density | Standard Deviation 1.01 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cell Benign | 0.35 normalized optical density | Standard Deviation 1.58 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-1 | Change From Baseline: Cell Adjacent | 1.59 normalized optical density | Standard Deviation 1.18 |
Comparison: Change from Baseline: IGF-1 Tumor (Cell)p-value: 0.128Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Benign (Nuc)p-value: 0.304Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Adjacent (Nuc)p-value: 0.23Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Tumor (Nuc)p-value: 0.298Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Benign (Cyt)p-value: 0.247Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Adjacent (Cyt)p-value: 0.093Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Tumor (Cyt)p-value: 0.066Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Benign (Cell)p-value: 0.247Wilcoxon rank-sum test
Comparison: Change from Baseline: IGF-1 Adjacent (Cell)p-value: 0.128Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: IGFBP-3
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Nuc Adjacent | 0.01 normalized optical density | Standard Deviation 1.51 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cyt Tumor | -1.09 normalized optical density | Standard Deviation 0.9 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cyt Benign | -0.38 normalized optical density | Standard Deviation 1.56 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cell Benign | -0.43 normalized optical density | Standard Deviation 2.02 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Nuc Tumor | 0.69 normalized optical density | Standard Deviation 2.21 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cell Adjacent | -0.24 normalized optical density | Standard Deviation 1.62 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cyt Adjacent | -0.96 normalized optical density | Standard Deviation 1.39 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cell Tumor | -0.14 normalized optical density | Standard Deviation 1.48 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Nuc Benign | -0.43 normalized optical density | Standard Deviation 2.77 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cell Tumor | 1.24 normalized optical density | Standard Deviation 0.79 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Nuc Benign | 0.78 normalized optical density | Standard Deviation 3.7 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Nuc Adjacent | 1.55 normalized optical density | Standard Deviation 1.9 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Nuc Tumor | 1.75 normalized optical density | Standard Deviation 1.79 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cyt Benign | 0.52 normalized optical density | Standard Deviation 1.26 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cyt Adjacent | 0.67 normalized optical density | Standard Deviation 0.9 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cyt Tumor | 0.76 normalized optical density | Standard Deviation 0.8 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cell Benign | 0.68 normalized optical density | Standard Deviation 2.39 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGFBP-3 | Change From Baseline: Cell Adjacent | 1.07 normalized optical density | Standard Deviation 1.13 |
Comparison: Change From Baseline: Nuc Benign p-valuep-value: 0.297Wilcoxon rank-sum test
Comparison: Change From Baseline: Nuc Adjacent p-valuep-value: 0.233Wilcoxon rank-sum test
Comparison: Change From Baseline: Nuc Tumor p-valuep-value: 0.371Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Benign p-valuep-value: 0.198Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Adjacent p-valuep-value: 0.233Wilcoxon rank-sum test
Comparison: Change From Baseline: Cyt Tumor p-valuep-value: 0.074Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Benign p-valuep-value: 0.234Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Adjacent p-valuep-value: 0.233Wilcoxon rank-sum test
Comparison: Change From Baseline: Cell Tumor p-valuep-value: 0.233Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: IGF-Rb
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Measurements for each are per nuclear (Nuc in results), cytoplasmic (Cyt in results), and cellular (Cell in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Nuc Adjacent | 0.62 normalized optical density | Standard Deviation 1.24 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cyt Tumor | 0.04 normalized optical density | Standard Deviation 1.45 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cyt Benign | 0.09 normalized optical density | Standard Deviation 1.35 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cell Benign | -0.19 normalized optical density | Standard Deviation 1.21 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Nuc Tumor | 0.63 normalized optical density | Standard Deviation 2 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cell Adjacent | 0.17 normalized optical density | Standard Deviation 0.85 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cyt Adjacent | -0.24 normalized optical density | Standard Deviation 0.71 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cell Tumor | 0.31 normalized optical density | Standard Deviation 1.63 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Nuc Benign | -0.50 normalized optical density | Standard Deviation 1.08 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cell Tumor | 0.73 normalized optical density | Standard Deviation 0.39 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Nuc Benign | -0.52 normalized optical density | Standard Deviation 1.03 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Nuc Adjacent | 0.32 normalized optical density | Standard Deviation 0.37 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Nuc Tumor | 0.88 normalized optical density | Standard Deviation 0.5 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cyt Benign | -0.48 normalized optical density | Standard Deviation 1.19 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cyt Adjacent | 0.80 normalized optical density | Standard Deviation 0.94 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cyt Tumor | 0.58 normalized optical density | Standard Deviation 0.42 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cell Benign | -0.52 normalized optical density | Standard Deviation 1.05 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: IGF-Rb | Change From Baseline: Cell Adjacent | 0.56 normalized optical density | Standard Deviation 0.52 |
Comparison: Change from Baseline: Nuc Benign p-valuep-value: 1Wilcoxon rank-sum test
Comparison: Change from Baseline: Nuc Adjacent p-valuep-value: 0.903Wilcoxon rank-sum test
Comparison: Change from Baseline: Nuc Tumor p-valuep-value: 1Wilcoxon rank-sum test
Comparison: Change from Baseline: Cyt Benign p-valuep-value: 0.269Wilcoxon rank-sum test
Comparison: Change from Baseline: Cyt Adjacent p-valuep-value: 0.066Wilcoxon rank-sum test
Comparison: Change from Baseline: Cyt Tumor p-valuep-value: 1Wilcoxon rank-sum test
Comparison: Change from Baseline: Cell Benign p-valuep-value: 0.425Wilcoxon rank-sum test
Comparison: Change from Baseline: Cell Adjacent p-valuep-value: 0.27Wilcoxon rank-sum test
Comparison: Change from Baseline: Cell Tumor p-valuep-value: 1Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: Ki-67
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: Ki-67 | Change From Baseline: Benign | 0.01 percent change | Standard Deviation 0.5 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: Ki-67 | Change From Baseline: Adjacent | -0.27 percent change | Standard Deviation 0.36 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: Ki-67 | Change From Baseline:Tumor | -6.40 percent change | Standard Deviation 12.11 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: Ki-67 | Change From Baseline:Tumor | 1.31 percent change | Standard Deviation 0.89 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: Ki-67 | Change From Baseline: Benign | 0.06 percent change | Standard Deviation 0.52 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: Ki-67 | Change From Baseline: Adjacent | -0.53 percent change | Standard Deviation 1.73 |
Comparison: Change from Baseline: Benign p-valuep-value: 0.865Wilcoxon rank-sum test
Comparison: Change from Baseline: Adjacent p-valuep-value: 1Wilcoxon rank-sum test
Comparison: Change from Baseline: Tumor p-valuep-value: 0.066Wilcoxon rank-sum test
Secondary
Change in Tissue Biomarker Levels: PSA
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core (benign in results), tumor tissue from a positive core (tumor in results), and normal tissue adjacent to tumor from a positive core (adjacent in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: Baseline to Week 52
Population: The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: PSA | Change From Baseline: Benign | 0.01 normalized optical density | Standard Deviation 0.42 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: PSA | Change From Baseline: Adjacent | -0.10 normalized optical density | Standard Deviation 0.09 |
| Group I (Pomegranate-extract Pill) | Change in Tissue Biomarker Levels: PSA | Change From Baseline: Tumor | 0.09 normalized optical density | Standard Deviation 0.39 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: PSA | Change From Baseline: Benign | 0.04 normalized optical density | Standard Deviation 0.21 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: PSA | Change From Baseline: Adjacent | 0.16 normalized optical density | Standard Deviation 0.43 |
| Group II (Placebo) | Change in Tissue Biomarker Levels: PSA | Change From Baseline: Tumor | 0.25 normalized optical density | Standard Deviation 0.52 |
Comparison: Benign core p-valuep-value: 0.344Wilcoxon rank-sum test
Comparison: Adjacent core p-valuep-value: 0.371Wilcoxon rank-sum test
Comparison: Tumor core p-valuep-value: 0.766Wilcoxon rank-sum test
Secondary
Change in Total Serum Prostate Specific Antigen (PSA) From Baseline
Time frame: Up to 1 year
Population: Statistician notes that serum PSA data is missing for one participant in the pomegranate extract arm for all time points, missing for another in the pomegranate arm at week 39, and one from the placebo arm at week 39.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change Baseline to Week 13 | -1.88 ng/mL | Standard Deviation 4.78 |
| Group I (Pomegranate-extract Pill) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change from Baseline Week 26 | -1.41 ng/mL | Standard Deviation 4.67 |
| Group I (Pomegranate-extract Pill) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change from Baseline Week 39 | -1.52 ng/mL | Standard Deviation 5.52 |
| Group I (Pomegranate-extract Pill) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change Baseline to Week 52 | -1.00 ng/mL | Standard Deviation 5.89 |
| Group II (Placebo) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change Baseline to Week 52 | -0.08 ng/mL | Standard Deviation 1.83 |
| Group II (Placebo) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change Baseline to Week 13 | -1.05 ng/mL | Standard Deviation 1.67 |
| Group II (Placebo) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change from Baseline Week 39 | -0.29 ng/mL | Standard Deviation 1.91 |
| Group II (Placebo) | Change in Total Serum Prostate Specific Antigen (PSA) From Baseline | Change from Baseline Week 26 | -0.77 ng/mL | Standard Deviation 1.33 |
Comparison: Change from Baseline PSA to Week 13p-value: 0.743Wilcoxon rank-sum test
Comparison: Change from Baseline PSA to Week 26p-value: 0.527Wilcoxon rank-sum test
Comparison: Change from Baseline PSA to Week 39p-value: 0.879Wilcoxon rank-sum test
Comparison: Change from Baseline PSA to Week 52p-value: 0.81Wilcoxon rank-sum test
Secondary
Compliance: Number of Participants Who Took Study Drug Per Protocol
Summarized by treatment arm with descriptive statistics, and tested for imbalance using Wilcoxon rank-sum test. Reported for each visit per protocol at Week 13, Week 26, Week 39, and Week 52 (end of study).
Time frame: Up to 1 year
Population: One participant has no compliance values for weeks 26 and 39.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Compliance: Number of Participants Who Took Study Drug Per Protocol | Week 13 | 14 Participants |
| Group I (Pomegranate-extract Pill) | Compliance: Number of Participants Who Took Study Drug Per Protocol | Week 26 | 14 Participants |
| Group I (Pomegranate-extract Pill) | Compliance: Number of Participants Who Took Study Drug Per Protocol | Week 39 | 14 Participants |
| Group I (Pomegranate-extract Pill) | Compliance: Number of Participants Who Took Study Drug Per Protocol | End of Study (Week 52) | 14 Participants |
| Group II (Placebo) | Compliance: Number of Participants Who Took Study Drug Per Protocol | End of Study (Week 52) | 15 Participants |
| Group II (Placebo) | Compliance: Number of Participants Who Took Study Drug Per Protocol | Week 13 | 14 Participants |
| Group II (Placebo) | Compliance: Number of Participants Who Took Study Drug Per Protocol | Week 39 | 14 Participants |
| Group II (Placebo) | Compliance: Number of Participants Who Took Study Drug Per Protocol | Week 26 | 14 Participants |
Secondary
Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE)
Patient toxicity throughout the study will be summarized in several ways; the presence or absence of any toxicity, worst CTCAE grade, and strongest investigator-defined relationship will all be examined and characterized by treatment arm, and analyzed appropriately (Wilcoxon rank-sum for ordinal data, Fisher's exact test for dichotomous data, and log rank test for time to event data).
Time frame: Up to 1 year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Any Adverse Event | 14 Participants |
| Group I (Pomegranate-extract Pill) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Multiple Adverse Events | 14 Participants |
| Group I (Pomegranate-extract Pill) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Grade 3 (Severe) or Worse | 3 Participants |
| Group I (Pomegranate-extract Pill) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Serious Adverse Events | 2 Participants |
| Group II (Placebo) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Serious Adverse Events | 2 Participants |
| Group II (Placebo) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Any Adverse Event | 13 Participants |
| Group II (Placebo) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Grade 3 (Severe) or Worse | 4 Participants |
| Group II (Placebo) | Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE) | Multiple Adverse Events | 11 Participants |
Secondary
Prostate Specific Antigen Doubling Time (PSA DT)
PSA DT will be determined from PSA values obtained during study participation (baseline and weeks 13, 26, 39 and 52). The secondary endpoint of PSA DT is based on the value at study completion (week 52 or at point of early termination). However, PSA DT will be determined starting at week 26 (the earliest time point with 3 values) and week 39 and recorded. PSA doubling time is a measure based on the slope of the PSA at multiple time points. If the slope is relatively flat, the predicted doubling time could be far beyond the length of the actual study. As such, the value is not limited to the time frame over which data is collected from the participant.
Time frame: up to 52 Weeks
Population: One of the participant's PSA values were 'non-detectable', therefore PSA observations could not be calculated for that participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Pomegranate-extract Pill) | Prostate Specific Antigen Doubling Time (PSA DT) | 134.01 weeks | Standard Deviation 560.33 |
| Group II (Placebo) | Prostate Specific Antigen Doubling Time (PSA DT) | 125.63 weeks | Standard Deviation 282.9 |
p-value: 0.58Wilcoxon rank-sum test