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

• ClinicalTrials.gov Identifier: NCT00927485
• Recruitment Status: Completed
• First Posted: June 25, 2009
• Results First Posted: December 16, 2020
• Last Update Posted: December 16, 2020
• Sponsor: University of Puerto Rico
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Marcia R. Cruz-Correa, MD, PhD, University of Puerto Rico

Tracking Information

• First Submitted Date: June 24, 2009
• First Posted Date: June 25, 2009
• Results First Submitted Date: November 18, 2020
• Results First Posted Date: December 16, 2020
• Last Update Posted Date: December 16, 2020
• Actual Study Start Date: November 2007
• Actual Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 18, 2020)

• Number of Polyps [ Time Frame: 5 years ]
  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.
• Size of Polyps [ Time Frame: 5 years ]
  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.

• Original Primary Outcome Measures (submitted: June 24, 2009): 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. [ Time Frame: 3-5 years ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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: 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Familial Adenomatous Polyposis

Intervention

• Drug: Calcumin (Curcumin)
  Patients will be randomized to curcumin (3 curcumin pills twice a day for 12 months).
  Other Name: Curcumin
• Other: Risk Factor Questionnaire
  Questions about current and past lifestyle, health background, and medications. This will take about 20 minutes.
• Other: Blood samples
  Three tubes of blood at visits 0, 4 and 12 months.
• Other: Biopsies (Sigmoidoscopy)
  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.
• Other: Biopsies (Upper endoscopy)
  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.

Study Arms

• Experimental: Curcumin
  Curcumin
  Interventions:

  • Drug: Calcumin (Curcumin)
  • Other: Risk Factor Questionnaire
  • Other: Blood samples
  • Other: Biopsies (Sigmoidoscopy)
  • Other: Biopsies (Upper endoscopy)
• Placebo Comparator: Placebo
  Placebo (sugar pills)
  Interventions:

  • Drug: Calcumin (Curcumin)
  • Other: Risk Factor Questionnaire
  • Other: Blood samples
  • Other: Biopsies (Sigmoidoscopy)
  • Other: Biopsies (Upper endoscopy)

• Publications *: Cruz-Correa M, Hylind LM, Marrero JH, Zahurak ML, Murray-Stewart T, Casero RA Jr, Montgomery EA, Iacobuzio-Donahue C, Brosens LA, Offerhaus GJ, Umar A, Rodriguez LM, Giardiello FM. Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology. 2018 Sep;155(3):668-673. doi: 10.1053/j.gastro.2018.05.031. Epub 2018 May 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 15, 2017): 44
• Original Estimated Enrollment (submitted: June 24, 2009): 50
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico

Administrative Information

• NCT Number: NCT00927485
• Other Study ID Numbers: Protocol A2210108-UPR
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Marcia R. Cruz-Correa, MD, PhD, University of Puerto Rico
• Study Sponsor: University of Puerto Rico
• Collaborators: National Institutes of Health (NIH)

Investigators

• Principal Investigator: Marcia R. Cruz-Correa, MD. PhD; University of Puerto Rico Comprehensive Cancer Center

• PRS Account: University of Puerto Rico
• Verification Date: November 2020