Curcumin in Treating Patients With Familial Adenomatous Polyposis
|ClinicalTrials.gov Identifier: NCT00641147|
Recruitment Status : Completed
First Posted : March 24, 2008
Results First Posted : September 29, 2017
Last Update Posted : September 29, 2017
|Condition or disease||Intervention/treatment||Phase|
|Familial Adenomatous Polyposis||Drug: Curcumin Other: Laboratory Biomarker Analysis Other: Placebo||Phase 2|
I. To determine in a randomized, double-blinded, placebo-controlled study the tolerability and effectiveness of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number, and polyp size in familial adenomatous polyposis patients with intact colons, ileorectal anastomosis surgery, or ileo-anal pullthrough (reservoir) surgery.
II. To measure markers of cell proliferation including colorectal mucosal levels of ornithine decarboxylase (ODC), polyamines, mucosal deoxyribonucleic acid (DNA) methylation, proliferative index (Ki67 antiproliferative cell nuclear antibody), apoptosis index, vascular density, mucosal prostaglandin, leukotriene levels, and activation of the nuclear factor kappa B (NFKB), and v-akt murine thymoma viral oncogene homolog 1 (Akt) survival pathways.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive curcumin orally (PO) twice daily (BID) for 12 months.
Arm II: Patients receive placebo PO BID for 12 months.
After completion of study treatment, patients are followed up at 4 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||November 2016|
|Actual Study Completion Date :||November 30, 2016|
Experimental: Arm I (curcumin)
Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis
Other: Laboratory Biomarker Analysis
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis
Other: Laboratory Biomarker Analysis
- Polyp Number [ Time Frame: Up to 12 months ]Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm
- Mean Polyp Size in mm [ Time Frame: Up to 12 months ]Mean size of the 5 largest polyps
- Number of Participants With a Decrease in Polyp Burden at 12 Months [ Time Frame: 12 months ]The polyp burden as evaluated by video tape review. Polyp burden at 12 months compared to time 0 for each participant and counting participants with decrease in polyp burden at 12 months.
- Number of Participants With Grade >=2 Adverse Events [ Time Frame: Up to 12 months ]
Events were graded as follows:
Grade 0= no adverse event or within normal limits; Grade 1= mild adverse event (causing no limitations of usual activity); Grade 2= moderate adverse event (causing some limitation of activity); Grade 3= severe adverse event (severe and undesirable; causing inability to carry out usual activities; Grade 4= life threatening or disabling adverse event; Grade 5= fatal adverse event.
- Medication Compliance [ Time Frame: Up to 12 months ]Medication compliance of the participant= number of capsules taken divided by the number of capsules prescribed as determined by pill count and described as a percentage per participant. Then the compliance of each participant in the assigned group (curcumin or placebo) was averaged together to obtain the medication compliance rate of that group.
- Change in Ornithine Decarboxylase (ODC) Activity Levels [ Time Frame: Baseline and 8 months ]Change in ODC mean activity levels (expressed as nmol of activity/mg of mucosal tissue/hr) at 8 months compared to baseline (time 0)
- Change in Total Polyamines Levels [ Time Frame: Baseline and 8 months ]Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline
- Change in Micro RNA 124-U6 (miR124-U6) [ Time Frame: Baseline and 8 months ]Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)
- Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT) [ Time Frame: Baseline and 8 months ]Change in SSAT mean activity level at 8 months compared to baseline (time 0)
- Change in Spermine Oxidase (SMOX) [ Time Frame: Baseline and 8months ]Change in SMOX mean activity level at 8 months compared to baseline (time 0)
- Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels [ Time Frame: Baseline up to 8 months ]Change in cellular proliferation rate was measured by assessment of Ki-67 anti-proliferative cell nuclear antibody index levels at 8 months
- Change in Apoptosis Index Levels [ Time Frame: 8 months ]Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement
- Change in Mucosal DNA Methylation Levels. [ Time Frame: Baseline to up to 12 months ]
- Change in Mucosal Leukotriene Levels. [ Time Frame: Baseline to up to 12 months. ]
- Change in Mucosal Prostaglandin Levels. [ Time Frame: Baseline to up to 12 months. ]
- Number of Patients Failing Study. [ Time Frame: Up to 16 months. ]Patients withdrawn from study due to increasing polyp burden and/or advancing histology.
- Change in Vascular Density [ Time Frame: Baseline up to 12 months ]
- Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway [ Time Frame: Baseline to 12 months ]
- Change in Akt Phosphorylation Levels [ Time Frame: Baseline up to 12 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00641147
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|University of Puerto Rico|
|San Juan, Puerto Rico, 00936|
|Principal Investigator:||Francis Giardiello||Johns Hopkins University/Sidney Kimmel Cancer Center|