Curcumin in Treating Patients With Familial Adenomatous Polyposis | oneFAPvoice

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completed

Curcumin in Treating Patients With Familial Adenomatous Polyposis

study id #: NCT00641147

condition: Familial Adenomatous Polyposis

status: Completed

purpose:

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: 50

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:

  • Change in activation of NFKB pathway [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in Akt phosphorylation levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in apoptosis index levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in Ki-67 anti-proliferative cell nuclear antibody index levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosa and adenoma histology assessed by light microscopy [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosal DNA methylation levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosal leukotriene levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosal prostaglandin levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in ODC activity levels expressed as nmol of activity/mg of musosal tissue/hr [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in polyamines levels expressed pg/mg protein [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in vascular density [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of grade >= 2 adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    A safety review will be performed at the time of interim analysis.
  • Mean polyp size in mm (mean size of the 5 largest polyps) [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
    Continuous variables relating to colorectal proliferation and polyp size will be compared in the two treatment groups by parametric statistics.
  • Medication compliance [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Number of patients failing study [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
  • Side effects of curcumin treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Total number of polyps [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
    The average number of polyps in the treatment groups will be compared by the t-test (or a distribution free analog if distribution assumptions are not met). Multivariate regression models will be used to adjust for strongly predictive factors that are not balanced in the treatment groups.

inclusion criteria:
- Patients with familial adenomatous polyposis who have undergone subtotal colectomy with ileorectal anastomosis, total coloctomy 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. s/p ileostomy

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

locations: Puerto Rico, United States