Healthy, no Evidence of Disease, Tobacco Use Disorder
Conditions
Brief summary
Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. Curcumin is a compound found in plants that may prevent colon cancer from forming. This phase II trial is studying how well curcumin works in preventing colon cancer in smokers with aberrant crypt foci.
Detailed description
PRIMARY OBJECTIVES: I. To determine mean percentage change from baseline in prostaglandin E2 (PGE2) within ACF pre and post 30 days of curcumin administration at a specified dose. SECONDARY OBJECTIVS: I. To determine mean percentage change from baseline in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF pre and post 30 days of curcumin administration at a specified dose. II. To determine mean percentage change from baseline in PGE2 and 5-HETE within comparison normal mucosa pre and post 30 days of curcumin administration at a specified dose. III. To quantify corresponding enzyme changes in the cyclooxygenases (COX-1, COX-2,) and lipoxygenase (5-LOX) protein abundance. Semi-quantitative changes in these proteins will be measured by western blotting and correlated with changes in prostaglandins and leukotrienes respectively. IV. Document changes in total ACF number. V. Determine proliferation by Ki-67 IHC in rectal mucosa pre and post therapy and correlate with changes in ACF number and size. VI. Determine curcumin concentration in rectal mucosa after 30 days therapy and correlate with PGE2 and 5-HETE changes described above. VII. Measure glutathione peroxidase (GPx) activity within the colon pre and post therapy as an indirect marker of reduced oxidative stress within the colonic epithelium. VIII. Ensure safety of all participants during course of study investigation. IX. Determine the curcumin concentration in plasma before and after treatment. OUTLINE: This is a multicenter, nonrandomized, uncontrolled study. Patients receive 1 of 2 doses of oral curcumin once daily. Treatment continues for 30 days in the absence of unacceptable toxicity or disease progression. Blood and tissue biopsies are obtained by sigmoidoscopy or colonoscopy at baseline and at day 30 for correlative biomarker studies. The change in prostaglandin E\_2 (PGE\_2) is assessed by enzyme immunoassay, 5-hydroxy-eicosatetraenoic acid (5-HETE) by high-performance liquid chromatography, cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) by western blotting, Ki-67 by immunohistochemistry, and glutathione peroxidase (GPx) by spectrophotometric assay. After completion of study therapy, patients are followed at 1 week. PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Interventions
OTHERlaboratory biomarker analysis
Correlative studies
OTHERpharmacological study
Correlative studies
DRUGcurcumin
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Current smoker with \> 3 pack-year total smoking history * Subjects taking NSAIDS or ASA \< 10 days month are eligible but must undergo 14 day washout and refrain from use during the study * Subjects who are: * Having a clinically indicated screening/surveillance colonoscopy (e.g. due to risk factors, personal history, or symptoms) OR * Not having a colonoscopy but are otherwise eligible. These subjects would undergo a flexible sigmoidoscopy. * ECOG performance status 0-2 (Karnofsky \> 60%) * No severe organ dysfunction which might increase bleeding risk: * Demonstrated by: Normal hematologic status (WBC \> 3,000/mm\^3, hemoglobin \> 10.0 gm/dl, and platelet-count \>100,000/mm\^3), normal hepatic function (bilirubin \< 1.5 mg/dl, transaminases \< 1.5x institutional norms), and normal renal function (serum creatinine \< 2.0 mg/dl, documented in clinical chart 28 days prior to enrollment * Healthy current smokers (1 cigarette in previous yr) with \> 3-pack year of cigarette smoking and able to provide written informed consent; there are no gender restrictions * The effects of curcumin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* NSAID or ASA use \> 10 days /month; any current glucocorticoid use or omega 3-fatty acid supplement use * Evidence of the following chronic medical conditions such as: * Pregnant or lactating women and/or women who are contemplating pregnancy during the duration of the protocol * History of chronic inflammatory bowel disease or prior pelvic irradiation * History of peptic ulcer disease (PUD) endoscopically confirmed \< 5 yrs from enrollment date * Newly diagnosed colorectal cancer or advanced adenoma \< 1 yr from enrollment * Unspecified history of bleeding or coagulation disorder reported by patient or in medical history * Hereditary Colon Cancer syndromes (FAP or HNPCC) * Participants may not be receiving any other investigational agents * History of contact dermatitis from turmeric * Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because curcumin is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with curcumin, breastfeeding should be discontinued if the mother is treated with curcumin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) | Baseline | Baseline prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue |
| Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) | At 30 day | Post-treatment prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) | At 30 Day | Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue |
| Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa | Baseline | Baseline prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue |
| Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa | At 30 day | Post-treatment prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue |
| Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa | Baseline | Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue |
| Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa | At 30 day | Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue |
| Change in Cyclooxygenases (COX-1, COX-2), and Lipoxygenase (5-LOX) Protein Abundance | Baseline to 30 days | The protein levels for each enzyme will be expressed as an absolute change from baseline and graphed against % change of its enzyme product in the same individual. The degree of correlation between these parameters will be assessed by either Pearson's correlation coefficient or Spearman's rank order correlation coefficient. |
| Changes in Total Aberrant Crypt Foci (ACF) Number | Baseline to 30 days | Changes in total aberrant crypt foci (ACF) number = Number of ACF at pre-treatment - Number of ACF at post-treatment |
| Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third | Baseline | — |
| Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third | Baseline | — |
| Number of Participants at Each Adverse Event Grade Level | Baseline to 30 days | — |
| Baseline Curcumin Concentration in Rectal Mucosa | Baseline | If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis. |
| Post-treatment Curcumin Concentration in Rectal Mucosa | At 30 day | If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis. |
| Baseline Curcumin Plasma Concentrations | Baseline | Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate. |
| Post-treatment Curcumin Plasma Concentrations | At 30 day | Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate. |
| Baseline Curcumin Conjugates Concentration in Rectal Mucosa | Baseline | If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis. |
| Post-treatment Curcumin Conjugates Concentration in Rectal Mucosa | At 30 day | If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis. |
| Baseline Curcumin Conjugates Plasma Concentrations | Baseline | Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate. |
| Post-treatment Curcumin Conjugates Plasma Concentrations | At 30 day | Post-treatment curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate. |
| Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third | Baseline | — |
| Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) | Baseline | Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue |
Countries
United States
Participant flow
Pre-assignment details
This is a 2-stage study. In Stage1, there are 23 enrolled participants who received 2 g curcumin. In Stage2, there are addictional 21 enrolled participants who received 4 g curcumin.
Participants by arm
| Arm | Count |
|---|---|
| Curcumin Stage 1: Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
Stage 2: Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
laboratory biomarker analysis: Correlative studies
pharmacological study: Correlative studies
curcumin: Given orally | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Curcumin |
|---|---|
| Age, Continuous Stage1 2 g (curcumin) N=22 | 57.1 years STANDARD_DEVIATION 5 |
| Age, Continuous Stage2 4 g (curcumin) N=21 | 52.2 years STANDARD_DEVIATION 6.8 |
| Sex/Gender, Customized Stage1 2 g (curcumin): Female | 13 participants |
| Sex/Gender, Customized Stage1 2 g (curcumin): Male | 9 participants |
| Sex/Gender, Customized Stage2 4 g (curcumin): Female | 12 participants |
| Sex/Gender, Customized Stage2 4 g (curcumin): Male | 9 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 22 | 11 / 21 |
| serious Total, serious adverse events | 0 / 22 | 1 / 21 |
Outcome results
Primary
Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)
Baseline prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants) and Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) | Stage1 2 g (curcumin) N=21 | 1.1 µg/g protein | Standard Deviation 1.8 |
| Curcumin | Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) | Stage2 4 g (curcumin) N=19 | 3.4 µg/g protein | Standard Deviation 4.8 |
Primary
Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)
Post-treatment prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue
Time frame: At 30 day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) | Stage1 2 g (curcumin) N=21 | 1.6 µg/g protein | Standard Deviation 1.8 |
| Curcumin | Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) | Stage2 4 g (curcumin) N=19 | 3.7 µg/g protein | Standard Deviation 3.2 |
Secondary
Baseline Curcumin Concentration in Rectal Mucosa
If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.
Time frame: Baseline
Population: Samples from 21 participants in the 2g curcumin arm and 18 participants in the 4g curcumin arm were sent to be assayed. Detectable levels of curcumin in rectal mucosa were found in 1 participant in the 2g arm and none in participants on the 4g arm. Therefore, only 1 sample from the 2g arm and 0 samples from the 4g arm are reported here.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Baseline Curcumin Concentration in Rectal Mucosa | 4.03 µg/g protein |
Secondary
Baseline Curcumin Conjugates Concentration in Rectal Mucosa
If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.
Time frame: Baseline
Population: Samples from 21 participants in the 2g curcumin arm and 19 participants in the 4g curcumin arm were sent to be assayed. Detectable levels of curcumin conjugates in rectal mucosa were found in 0 participants in the 2g arm and 1 participant on the 4g arm. Therefore, 0 samples from the 2g arm and 1 sample from the 4g arm are reported here.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Baseline Curcumin Conjugates Concentration in Rectal Mucosa | 4.21 µg/g protein |
Secondary
Baseline Curcumin Conjugates Plasma Concentrations
Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.
Time frame: Baseline
Population: Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 19 participants in the 4g arm; therefore, 19 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin | Baseline Curcumin Conjugates Plasma Concentrations | 15.8 µg/mL | Standard Deviation 14.8 |
Secondary
Baseline Curcumin Plasma Concentrations
Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.
Time frame: Baseline
Population: Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 4 participants in the 4g arm; therefore, 4 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin | Baseline Curcumin Plasma Concentrations | 7.3 µg/mL | Standard Deviation 8.1 |
Secondary
Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa
Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa | Stage1 2 g (curcumin) N=21 | 2.3 µg/g protein | Standard Deviation 1.3 |
| Curcumin | Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa | Stage2 4 g (curcumin) N=19 | 2.5 µg/g protein | Standard Deviation 1.5 |
Secondary
Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)
Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) | Stage1 2 g (curcumin) N=21 | 1.4 µg/g protein | Standard Deviation 0.9 |
| Curcumin | Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) | Stage2 4 g (curcumin) N=19 | 2.3 µg/g protein | Standard Deviation 1.6 |
Secondary
Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa
Baseline prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa | Stage1 2 g (curcumin) N=21 | 2.1 µg/g protein | Standard Deviation 3.2 |
| Curcumin | Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa | Stage2 4 g (curcumin) N=19 | 2.7 µg/g protein | Standard Deviation 1.9 |
Secondary
Change in Cyclooxygenases (COX-1, COX-2), and Lipoxygenase (5-LOX) Protein Abundance
The protein levels for each enzyme will be expressed as an absolute change from baseline and graphed against % change of its enzyme product in the same individual. The degree of correlation between these parameters will be assessed by either Pearson's correlation coefficient or Spearman's rank order correlation coefficient.
Time frame: Baseline to 30 days
Population: There is not enough tissue for the analysis, so no data is provided.
Secondary
Changes in Total Aberrant Crypt Foci (ACF) Number
Changes in total aberrant crypt foci (ACF) number = Number of ACF at pre-treatment - Number of ACF at post-treatment
Time frame: Baseline to 30 days
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Curcumin | Changes in Total Aberrant Crypt Foci (ACF) Number | Stage1 2 g (curcumin) N=22 | 0.0 Number of ACF |
| Curcumin | Changes in Total Aberrant Crypt Foci (ACF) Number | Stage2 4 g (curcumin) N=19 | 6.0 Number of ACF |
Secondary
Number of Participants at Each Adverse Event Grade Level
Time frame: Baseline to 30 days
Population: These participants completed the study. The data is from the final dataset which was available in 2013 following the publication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Curcumin | Number of Participants at Each Adverse Event Grade Level | 2 g (curcumin) N=22: No AE reported | 10 participants |
| Curcumin | Number of Participants at Each Adverse Event Grade Level | 2 g (curcumin) N=22: AE with a grade of 1 or 2 | 12 participants |
| Curcumin | Number of Participants at Each Adverse Event Grade Level | 2 g (curcumin) N=22: AE with a grade of 3 | 0 participants |
| Curcumin | Number of Participants at Each Adverse Event Grade Level | 4 g (curcumin) N=19: No AE reported | 8 participants |
| Curcumin | Number of Participants at Each Adverse Event Grade Level | 4 g (curcumin) N=19: AE with a grade of 1 or 2 | 10 participants |
| Curcumin | Number of Participants at Each Adverse Event Grade Level | 4 g (curcumin) N=19: AE with a grade of 3 | 1 participants |
Secondary
Post-treatment Curcumin Concentration in Rectal Mucosa
If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.
Time frame: At 30 day
Population: The analysis is based on 39 participants (21 participants from 2g curcmin, and 18 participants from 4 g curcumin). In 2g group, a total of 5 samples with detectable levels were analyzed. In 4g group, a total of 3 samples with detectable levels were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Post-treatment Curcumin Concentration in Rectal Mucosa | 2 g (curcumin) N=21 subjects, N=5 samples analyzed | 8.2 µg/g protein | Standard Deviation 2.9 |
| Curcumin | Post-treatment Curcumin Concentration in Rectal Mucosa | 4 g (curcumin) N=18 subjects, N=3 samples analyzed | 3.8 µg/g protein | Standard Deviation 0.6 |
Secondary
Post-treatment Curcumin Conjugates Concentration in Rectal Mucosa
If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.
Time frame: At 30 day
Population: The analysis is based on 39 participants (21 participants from 2g curcumin group and 18 participatns from 4g curcumin group). In 2g group, a total of 13 samples with detectable levels were analyzed. In 4g group, a total of 12 samples with detectable levels were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Post-treatment Curcumin Conjugates Concentration in Rectal Mucosa | 4 g (curcumin) N=18 subjects, N=12 samples | 4.5 µg/g protein | Standard Deviation 1.7 |
| Curcumin | Post-treatment Curcumin Conjugates Concentration in Rectal Mucosa | 2 g (curcumin) N=21 subjects, N=13 samples | 5.9 µg/g protein | Standard Deviation 2.6 |
Secondary
Post-treatment Curcumin Conjugates Plasma Concentrations
Post-treatment curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.
Time frame: At 30 day
Population: Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 19 participants in the 4g arm; therefore, 19 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin | Post-treatment Curcumin Conjugates Plasma Concentrations | 78.5 µg/mL | Standard Deviation 84.3 |
Secondary
Post-treatment Curcumin Plasma Concentrations
Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.
Time frame: At 30 day
Population: Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 2 participants in the 4g arm; therefore, 2 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin | Post-treatment Curcumin Plasma Concentrations | 3.8 µg/mL | Standard Deviation 1.3 |
Secondary
Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa
Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue
Time frame: At 30 day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa | Stage1 2 g (curcumin) N=21 | 2.4 µg/g protein | Standard Deviation 1.2 |
| Curcumin | Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa | Stage2 4 g (curcumin) N=19 | 2.2 µg/g protein | Standard Deviation 1.6 |
Secondary
Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)
Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue
Time frame: At 30 Day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) | Stage1 2 g (curcumin) N=21 | 1.4 µg/g protein | Standard Deviation 1 |
| Curcumin | Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) | Stage2 4 g (curcumin) N=19 | 1.9 µg/g protein | Standard Deviation 0.9 |
Secondary
Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa
Post-treatment prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue
Time frame: At 30 day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa | Stage1 2 g (curcumin) N=21 | 2.7 µg/g protein | Standard Deviation 3.7 |
| Curcumin | Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa | Stage2 4 g (curcumin) N=19 | 2.6 µg/g protein | Standard Deviation 2.9 |
Secondary
Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 17 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third | Stage1 2 g (curcumin) N=22 | 25.2 percentage of labeled cells | Standard Deviation 5.3 |
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third | Stage2 4 g (curcumin) N=17 | 28.7 percentage of labeled cells | Standard Deviation 9.1 |
Secondary
Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third
Time frame: At 30 day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third | Stage1 2 g (curcumin) N=22 | 23.5 percentage of labeled cells | Standard Deviation 8 |
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third | Stage2 4 g (curcumin) N=19 | 30.9 percentage of labeled cells | Standard Deviation 7.7 |
Secondary
Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third
Time frame: At 30 day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third | Stage1 2 g (curcumin) N=22 | 11.8 percentage of labeled cells | Standard Deviation 7.2 |
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third | Stage2 4 g (curcumin) N=19 | 16.4 percentage of labeled cells | Standard Deviation 10.3 |
Secondary
Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin : (N = 17 participants).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third | Stage1 2 g (curcumin) N=22 | 11.9 percentage of labeled cells | Standard Deviation 4.2 |
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third | Stage2 4 g (curcumin) N=17 | 12.8 percentage of labeled cells | Standard Deviation 6.1 |
Secondary
Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third
Time frame: Baseline
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 17 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third | Stage1 2 g (curcumin) N=22 | 0.5 percentage of labeled cells | Standard Deviation 0.9 |
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third | Stage2 4 g (curcumin) N=17 | 0.3 percentage of labeled cells | Standard Deviation 0.6 |
Secondary
Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third
Time frame: At 30 day
Population: The analysis is based on participants whose data are evaluable and available. Stage1 2 g crucumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third | Stage1 2 g (curcumin) N=22 | 0.6 percentage of labeled cells | Standard Deviation 1.4 |
| Curcumin | Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third | Stage 2 4 g (curcumin) N=19 | 0.3 percentage of labeled cells | Standard Deviation 0.8 |