Prostate Cancer
Conditions
Brief summary
The purpose of this study is to look at the effect that the study drug OPC has on AGE levels in patients with prostate cancer.
Detailed description
AGEs are a type of metabolite, or substance, found in the food. The AGE content in food is determined by the types of food you eat and also how you prepare your food. The researchers helping conduct this study have found a potential link between AGE levels and cancer. The purpose of this study is to see if Oligomeric Procyanidin Complex (OPC) has an effect on the AGE levels in your blood and to see if those AGE levels have an effect on your cancer.
Interventions
DRUGMetformin
OTHEROPC
OPC is a derivative of grape seed extract
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmation of adenocarcinoma of the prostate that is documented by one of the following: pathology report or clinic note with documented history of prostate cancer. 2. Subjects must be receiving ADT with a GnRH agonist or antagonist, with or without an anti-androgen, with a current testosterone level documented to be \<50ng/dL at enrollment. Subjects whose ADT is interrupted may enroll or continue on study as long as the testosterone is documented to remain \<50ng/dL for the entire duration of study participation. Subjects who have undergone orchiectomy are also eligible. 3. Prior cytotoxic chemotherapy for metastatic prostate cancer; prior treatment with genomically-targeted agents, or Provenge is allowed. 4. Subjects must have adequate hematologic, renal, and hepatic function at baseline, as follows: * Hematology parameters: ANC \>1000/mcL, platelets \> 100,000/mcL, Hgb \>8.0gm/dL * Renal Function: eGFR of \> 45mls/min using Cockgroft and Gault formula (see appendix C). * Liver Function: Total bilirubin ≤ULN, AST and ALT \<1.5xULN 5. Able to swallow and retain oral medication 6. ECOG performance status of 0 - 2 7. Ability to sign written informed consent 8. Testosterone level \<50ng/dL
Exclusion criteria
1. Known allergy to grapes or grape seed 2. History of receiving more than 2 classes of ADT. 3. Current use of strong antioxidants (extracts from grape seed, milk thistle; pine bark, green tea, saw palmetto; resveratrol; flavonoids; catechins; ellagic acid), large quantities of red grapes, white button mushrooms, red wine. See section 4.7 for more details.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AGE Level Reduction | 85 days | The primary objective is to determine if any of the test agent are able to reduce AGE levels by an average of 30% (or greater) in 50% or more of test subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Changes to AGE Level and Changes to PSA | 85 days | To assess whether changes in plasma AGE levels correlate with changes in PSA levels over the 85-day study period |
| Correlation Between Changes to AGE Level and Changes to BMI | 85 days | This outcome was intended to evaluate whether changes in plasma AGE levels from baseline to Day 85 correlated with changes in body mass index (BMI), planned for Screening, Day 1, and Day 85. Although this measure was protocol-specified, BMI assessments were never initiated because clinical research personnel responsible for baseline and follow-up measurements departed early in the study period, before any participants reached these scheduled assessment points. After this loss of personnel, the study team no longer had qualified staff to perform BMI measurements, and retrospective collection was not possible. As a result, no BMI data were collected for any participants. |
| Correlation Between Changes to AGE Level and Changes to Insulin Resistance (HOMA-IR) | 85 days | — |
| Correlation Between Changes to AGE Level and Changes to A1C. | 85 days | — |
| Correlations Between Changes to AGE Level and Changes to Testosterone. | 85 days | — |
| Correlation Between Changes to AGE Level and Changes to Lipids. | 85 days | — |
| Correlation Between Changes to AGE Level and Changes to Diet | 85 days | This outcome aimed to determine whether changes in plasma AGE levels correlated with changes in dietary intake, assessed using the NIH "Eating at America's Table Study Quick Food Scan" and the NCI "Quick Food Scan" at baseline and Day 85. Although protocol-specified, these instruments were never administered because essential study personnel who were responsible for conducting participant-reported assessments left the study before any questionnaire sessions occurred. After staff departure, the study team lacked the resources required to administer or score the diet questionnaires, and no alternative personnel were available. As a result, no dietary intake data were collected, and no analyses could be performed. |
| Correlation Between Changes to AGE Level and Changes to Quality of Life | 85 days | This outcome sought to evaluate whether changes in plasma AGE levels correlated with changes in quality of life, assessed with the FACT-P and AUA Symptom Index at baseline and Day 85. Although these assessments were included in the protocol, they were never initiated because the study personnel responsible for administering participant-reported questionnaires departed before any QOL data collection sessions were conducted. After the loss of staff, the study team did not have qualified personnel to administer, process, or score QOL instruments, making further collection infeasible. Consequently, no QOL data were collected for any participants. |
| Frequency of Adverse Events as Assessed by CTCAE v. 4 | 85 days | To assess the frequency and severity of adverse events associated with study drug administration, categorized by CTCAE v4 criteria. |
| Correlation Between AGE Levels and Plasma IL6 | 85 days | — |
| Correlation Between AGE Levels and Leptin | 85 days | — |
| Correlation Between AGE Levels and C-reactive Protein (CRP) | 85 days | — |
| Correlation Between AGE Levels and Malondialdehyde (MDA) | 85 days | — |
| Correlation Between AGE Levels and oxLDLs (Low Density Lipoprotein) | 85 days | — |
| Correlation Between AGE Levels and sRAGE (Soluble Receptor for AGE) | 85 days | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael Lilly, MD
Medical University of South Carolina
Participant flow
Pre-assignment details
Overall 14 non-evaluable
Participants by arm
| Arm | Count |
|---|---|
| Metformin Only Subjects will be supplied with metformin tablets850mg. During the ramp up phase subjects will take metformin in the morning. During weeks 2-12 the metformin tablet will be taken approximately 12 hours apart.
Metformin | 12 |
| OPC Only Subjects will take one OPC capsule at the same time each morning and evening, approximately 12 hours apart during weeks 1-12.
OPC: OPC is a derivative of grape seed extract | 16 |
| Metformin Plus OPC During week 1, subjects will take one metformin tablet in the morning and one OPC tablet in the morning and in the evening, about12 hours apart.
During weeks 2-12 the metformin tablet will betaken approximately 12 hours apart and one OPC about 12 hours apart, in the morning and in the evening.
Metformin
OPC: OPC is a derivative of grape seed extract | 13 |
| Total | 41 |
Baseline characteristics
| Characteristic | Metformin Only | OPC Only | Metformin Plus OPC | Total |
|---|---|---|---|---|
| Age, Continuous | 70.4 years STANDARD_DEVIATION 6.1 | 73.6 years STANDARD_DEVIATION 5 | 74.9 years STANDARD_DEVIATION 7.8 | 73.1 years STANDARD_DEVIATION 6.4 |
| Race/Ethnicity, Customized Black/AA | 5 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 15 Participants | 11 Participants | 33 Participants |
| Region of Enrollment United States | 12 participants | 16 participants | 13 participants | 41 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 16 Participants | 13 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 16 | 0 / 13 |
| other Total, other adverse events | 9 / 12 | 4 / 16 | 9 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 16 | 0 / 13 |
Outcome results
Primary
AGE Level Reduction
The primary objective is to determine if any of the test agent are able to reduce AGE levels by an average of 30% (or greater) in 50% or more of test subjects.
Time frame: 85 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metformin Only | AGE Level Reduction | 1.49 ng/ml |
| OPC Only | AGE Level Reduction | 0.49 ng/ml |
| Metformin Plus OPC | AGE Level Reduction | 0.8 ng/ml |
Secondary
Correlation Between AGE Levels and C-reactive Protein (CRP)
Time frame: 85 days
Secondary
Correlation Between AGE Levels and Leptin
Time frame: 85 days
Secondary
Correlation Between AGE Levels and Malondialdehyde (MDA)
Time frame: 85 days
Secondary
Correlation Between AGE Levels and oxLDLs (Low Density Lipoprotein)
Time frame: 85 days
Secondary
Correlation Between AGE Levels and Plasma IL6
Time frame: 85 days
Secondary
Correlation Between AGE Levels and sRAGE (Soluble Receptor for AGE)
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to A1C.
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to BMI
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to Diet.
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to Insulin Resistance (HOMA-IR)
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to Lipids.
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to PSA
Time frame: 85 days
Secondary
Correlation Between Changes to AGE Level and Changes to Quality of Life
Time frame: 85 days
Secondary
Correlations Between Changes to AGE Level and Changes to Testosterone.
Time frame: 85 days
Secondary
Frequency of Adverse Events as Assessed by CTCAE v. 4
Toxicities will be tabulated per arm by type and grade and the proportion of patients with grade 3, grade 4 or an SAE will be estimated with a 90% confidence interval.
Time frame: 85 days