Familial Adenomatous Polyposis
Conditions
Keywords
Familial Adenomatous Polyposis (FAP), Curcumin, Colorectal polyps, Duodenal polyps
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.
Interventions
DRUGCalcumin (Curcumin)
Patients will be randomized to curcumin (3 curcumin pills twice a day for 12 months).
Questions about current and past lifestyle, health background, and medications. This will take about 20 minutes.
OTHERBlood samples
Three tubes of blood at visits 0, 4 and 12 months.
OTHERBiopsies (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.
OTHERBiopsies (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.
Sponsors
National Institutes of Health (NIH)
University of Puerto Rico
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Polyps | 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 | 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. |
Countries
Puerto Rico
Participant flow
Recruitment details
The study was conducted from September 2011 to November 2016 at the Johns Hopkins Hospital and the University of Puerto Rico Medical Sciences Campus. Participants were identified and recruited from the Johns Hopkins Polyposis Registry or from the University of Puerto Rico Familial Colorectal Cancer Registry.
Pre-assignment details
Absence of effective birth control; pregnancy; WBC \< 3500/ml; platelet \< 100,000/ml, BUN \> 25 mg/dl, Creat \> 1.5 mg/dl; malignancy; unwillingness to discontinue NSAIDs; active reflux; hx of peptic ulcer; active bacterial infection; use of warfarin or antiplatelets; allergy to curcumin. 3 month washout period for individuals taking NSAIDs, curcumin, turmeric, aspirin, calcium, vitamin D, green tea or polyphenol E
Participants by arm
| Arm | Count |
|---|---|
| Curcumin Curcumin
Calcumin (Curcumin): Patients will be randomized to curcumin (3 curcumin pills twice a day for 12 months).
Risk Factor Questionnaire: Questions about current and past lifestyle, health background, and medications. This will take about 20 minutes.
Blood samples: Three tubes of blood at visits 0, 4 and 12 months.
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.
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. | 21 |
| Placebo Placebo (sugar pills)
Calcumin (Curcumin): Patients will be randomized to curcumin (3 curcumin pills twice a day for 12 months).
Risk Factor Questionnaire: Questions about current and past lifestyle, health background, and medications. This will take about 20 minutes.
Blood samples: Three tubes of blood at visits 0, 4 and 12 months.
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.
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. | 23 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | noncompliance, prophylactic surgery, inc | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Curcumin | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants | 21 Participants | 23 Participants |
| Age, Continuous | 41.6 Years STANDARD_DEVIATION 1 | 44.5 Years STANDARD_DEVIATION 1 | 38.7 Years STANDARD_DEVIATION 1 |
| Region of Enrollment Puerto Rico | 44 participants | 21 participants | 23 participants |
| Sex: Female, Male Female | 28 Participants | 14 Participants | 14 Participants |
| Sex: Female, Male Male | 16 Participants | 7 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 21 | 5 / 23 |
| serious Total, serious adverse events | 0 / 21 | 0 / 23 |
Outcome results
Primary
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.
Time frame: 5 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Number of Polyps | 18.6 Number of Polyps |
| Placebo | Number of Polyps | 22.6 Number of Polyps |
Primary
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.
Time frame: 5 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Curcumin | Size of Polyps | 2.3 mm |
| Placebo | Size of Polyps | 2.1 mm |