Curcumin in Treating Patients With Familial Adenomatous Polyposis

study id #: NCT00641147

condition: Familial Adenomatous Polyposis

status: completed

This clinical 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.

intervention:
Drug: Curcumin
Other: Laboratory Biomarker Analysis
Other: Placebo

start date: October 2010

estimated completion: November 2016

last updated: September 29, 2017

phase of development: Phase 2

size / enrollment: 44

study design:
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

study description:
PRIMARY OBJECTIVES: 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 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 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.

primary outcomes:

• 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

secondary outcomes:

• 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

inclusion criteria:

exclusion criteria:
- Female patients of childbearing age not on effective birth control
- Pregnant women
- WBC < 3500/ml
- Platelet count < 100,000/ml
- BUN > 25mg%
- Creatinine > 1.5mg%
- Patients unable to stop 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 GERD (symptomatic despite medication or current erosive esophagitis on endoscopy)
- Patients with a history of peptic ulcer disease
- Patients on Warfarin or Plavix

sponsor: National Cancer Institute (NCI)

investigators: Francis Giardiello

trial center locations: Puerto Rico, United States