Clinical trial NCT00641147: Curcumin in Treating Patients With Familial Adenomatous Polyposis
Official title: Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Familial Adenomatous Polyposis
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-03-24
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Polyp Number
timeFrame: Up to 12 months
Secondary outcomes:
measure: Mean Polyp Size in mm
timeFrame: Up to 12 months
measure: Number of Participants With a Decrease in Polyp Burden at 12 Months
timeFrame: 12 months
measure: Number of Participants With Grade >=2 Adverse Events
timeFrame: Up to 12 months
measure: Medication Compliance
timeFrame: Up to 12 months
measure: Change in Ornithine Decarboxylase (ODC) Activity Levels
timeFrame: Baseline and 8 months
measure: Change in Total Polyamines Levels
timeFrame: Baseline and 8 months
measure: Change in Micro RNA 124-U6 (miR124-U6)
timeFrame: Baseline and 8 months
measure: Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)
timeFrame: Baseline and 8 months
measure: Change in Spermine Oxidase (SMOX)
timeFrame: Baseline and 8months
measure: Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels
timeFrame: Baseline up to 8 months
measure: Change in Apoptosis Index Levels
timeFrame: 8 months
Other outcomes:
measure: Change in Mucosal DNA Methylation Levels.
timeFrame: Baseline to up to 12 months
measure: Change in Mucosal Leukotriene Levels.
timeFrame: Baseline to up to 12 months.
measure: Change in Mucosal Prostaglandin Levels.
timeFrame: Baseline to up to 12 months.
measure: Number of Patients Failing Study.
timeFrame: Up to 16 months.
measure: Change in Vascular Density
timeFrame: Baseline up to 12 months
measure: Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway
timeFrame: Baseline to 12 months
measure: Change in Akt Phosphorylation Levels
timeFrame: Baseline up to 12 months
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Johns Hopkins University/Sidney Kimmel Cancer Center
name: Francis Giardiello
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.