Curcumin in Treating Patients With Familial Adenomatous Polyposis
- Conditions
- Familial Adenomatous Polyposis
- Interventions
- Registration Number
- NCT00641147
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase II trial studies curcumin in treating patients with familial adenomatous polyposis. Curcumin may prevent colorectal cancer in patients with a history of rectal polyps or colorectal neoplasia.
- Detailed Description
Specific Aims:
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- Patients with familial adenomatous polyposis who have undergone subtotal colectomy with ileorectal anastomosis, total colectomy with ileo-anal pull through (reservoir), and patients with intact colons with 5 or more adenomas in the rectum-sigmoid or reservoir
- Patients with familial adenomatous polyposis (FAP) and duodenal adenomatous polyposis without current lower tract adenomatous polyposis i.e. status/post (s/p) ileostomy
- Female patients of childbearing age not on effective birth control
- Pregnant women
- White blood cell count (WBC) < 3500/ml
- Platelet count < 100,000/ml
- Blood urea nitrogen (BUN) > 25mg%
- Creatinine > 1.5mg%
- Patients unable to stop non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, curcumin, tumeric, calcium, vitamin D, green tea, or polyphenol E supplements for the duration of the trial
- Malignancy other than nonmelanoma skin cancer
- Active bacterial infection
- Patients with symptoms of active gastroesophageal reflux disease (GERD) (symptomatic despite medication or current erosive esophagitis on endoscopy)
- Patients with a history of peptic ulcer disease
- Patients on warfarin or plavix
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II (placebo) Laboratory Biomarker Analysis Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis Arm I (curcumin) Laboratory Biomarker Analysis Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis Arm II (placebo) Placebo Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis Arm I (curcumin) Curcumin Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis
- Primary Outcome Measures
Name Time Method Polyp Number 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
- Secondary Outcome Measures
Name Time Method Number of Participants With a Decrease in Polyp Burden at 12 Months 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.
Medication Compliance 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 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 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) Baseline and 8 months Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)
Mean Polyp Size in mm Up to 12 months Mean size of the 5 largest polyps
Change in Spermine Oxidase (SMOX) Baseline and 8months Change in SMOX mean activity level at 8 months compared to baseline (time 0)
Number of Participants With Grade >=2 Adverse Events 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.Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT) Baseline and 8 months Change in SSAT mean activity level at 8 months compared to baseline (time 0)
Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels 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 8 months Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement
Trial Locations
- Locations (2)
University of Puerto Rico
🇵🇷San Juan, Puerto Rico
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States