Curcumin in Treating Patients With Familial Adenomatous Polyposis

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.

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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