Use of Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)

Study Overview
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Brief Summary
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Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder characterized by the formation of multiple adenomatous colorectal polyps usually in the teenage years. Virtually, all patients with FAP will develop colorectal cancer on average by the 5th decade of life if prophylactic surgery is not performed. Besides, these individuals must have lifelong cancer surveillance of the remaining colorectum or ileum. Use of nonsteroidal anti-inflammatory drug (NSAID), such as sulindac, or celecoxib, which selectively inhibits prostaglandin synthesis primarily via the inhibition of cyclogenase-2 (COX-2) have been shown to reduce the incidence and induce regression of adenomas in the rectum of patients with FAP. However, use of NSAIDs and COX-2 inhibitors is associated with significant comorbidity including renal and gastric toxicity and increased risk of vascular events. Therefore, identification of a chemopreventive agent that would have similar efficacy but less toxicity would enhance our ability to treat these patients. Therefore the following specific aim has been proposed:To determine in a randomized, double-blinded, placebo-controlled study the tolerability and efficacy of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number, and polyp size in patients with FAP.

Detailed Description
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Patients will be randomized to curcumin (2 curcumin pills twice a day for 12 months) or placebo (2 pills twice a day for 12 months). Besides, blood samples, risk factor questionnaire,and biopsies (upper endoscopy and sigmoidoscopy) will be obtained.

Official Title
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Use of Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)

Conditions
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Familial Adenomatous Polyposis

Intervention / Treatment
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* Drug: Calcumin (Curcumin)
* Other: Risk Factor Questionnaire
* Other: Blood samples
* Other: Biopsies (Sigmoidoscopy)
* Other: Biopsies (Upper endoscopy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21-85 years with FAP (with an intact colon or who have had surgery) Exclusion Criteria: Mentally incompetent Female patients of childbearing age not on effective birth control Patients with WBC < 3,500/ml, platelet count < 100,000/ml, BUN > 25mg%, creatinine > 1.5mg% Patients unable to stop NSAIDS or aspirin use for the duration of the study Malignancy other than nonmelanoma skin cancer Active bacterial infection Patients with GERD (Gastro esophageal reflux disease) Patients with a history of peptic (stomach or duodenal) ulcer disease Patients on Warfarin or anti-platelet drugs

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curcumin<br>Curcumin | Drug: Calcumin (Curcumin)<br>* Patients will be randomized to curcumin (3 curcumin pills twice a day for 12 months).<br>* Other names: Curcumin;Other: Risk Factor Questionnaire<br>* Questions about current and past lifestyle, health background, and medications. This will take about 20 minutes.<br>Other: Blood samples<br>* Three tubes of blood at visits 0, 4 and 12 months.<br>Other: Biopsies (Sigmoidoscopy)<br>* Flexible sigmoidoscopy at baseline and every 4 months for the length of the study (4 months, 8 months, 12 months and 16 months). We will take 2-4 tissue samples of the colon lining by a pinch biopsy.<br>Other: Biopsies (Upper endoscopy)<br>* Other: Biopsies (Upper endoscopy) Upper endoscopy at baseline and at 12 months. We will take 2-4 tissue samples of the small intestine lining by a pinch biopsy.<br>|
| Placebo Comparator: Placebo<br>Placebo (sugar pills) | Drug: Calcumin (Curcumin)<br>* Patients will be randomized to curcumin (3 curcumin pills twice a day for 12 months).<br>* Other names: Curcumin;Other: Risk Factor Questionnaire<br>* Questions about current and past lifestyle, health background, and medications. This will take about 20 minutes.<br>Other: Blood samples<br>* Three tubes of blood at visits 0, 4 and 12 months.<br>Other: Biopsies (Sigmoidoscopy)<br>* Flexible sigmoidoscopy at baseline and every 4 months for the length of the study (4 months, 8 months, 12 months and 16 months). We will take 2-4 tissue samples of the colon lining by a pinch biopsy.<br>Other: Biopsies (Upper endoscopy)<br>* Other: Biopsies (Upper endoscopy) Upper endoscopy at baseline and at 12 months. We will take 2-4 tissue samples of the small intestine lining by a pinch biopsy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Polyps | To determine in a randomized, double-blinded, placebo-controlled study the tolerability and efficacy of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number in patients with FAP. | 5 years | 
| Size of Polyps | To determine in a randomized, double-blinded, placebo-controlled study the tolerability and efficacy of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp size in patients with FAP. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Adenomatous Polyposis (FAP), Curcumin, Colorectal polyps, Duodenal polyps