Curcumin in Treating Patients With Familial Adenomatous Polyposis

Familial Adenomatous Polyposis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00641147
• Other study ID #: NCI-2013-00536
• Secondary ID: NCI-2013-00536CD
• Status: Completed
• Phase: Phase 2
• First received: March 17, 2008
• Last updated: September 27, 2017
• Start date: October 2010
• Est. completion date: November 30, 2016

Study information

• Verified date: September 2017
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: November 30, 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli
• Colorectal Neoplasms
• Familial Adenomatous Polyposis
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Curcumin
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Placebo
Given PO

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico	San Juan
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Mucosal DNA Methylation Levels.		Baseline to up to 12 months
Other	Change in Mucosal Leukotriene Levels.		Baseline to up to 12 months.
Other	Change in Mucosal Prostaglandin Levels.		Baseline to up to 12 months.
Other	Number of Patients Failing Study.	Patients withdrawn from study due to increasing polyp burden and/or advancing histology.	Up to 16 months.
Other	Change in Vascular Density		Baseline up to 12 months
Other	Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway		Baseline to 12 months
Other	Change in Akt Phosphorylation Levels		Baseline up to 12 months
Primary	Polyp Number	Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm	Up to 12 months
Secondary	Mean Polyp Size in mm	Mean size of the 5 largest polyps	Up to 12 months
Secondary	Number of Participants With a Decrease in Polyp Burden at 12 Months	The polyp burden as evaluated by video tape review. Polyp burden at 12 months compared to time 0 for each participant and counting participants with decrease in polyp burden at 12 months.	12 months
Secondary	Number of Participants With Grade >=2 Adverse Events	Events were graded as follows: Grade 0= no adverse event or within normal limits; Grade 1= mild adverse event (causing no limitations of usual activity); Grade 2= moderate adverse event (causing some limitation of activity); Grade 3= severe adverse event (severe and undesirable; causing inability to carry out usual activities; Grade 4= life threatening or disabling adverse event; Grade 5= fatal adverse event.	Up to 12 months
Secondary	Medication Compliance	Medication compliance of the participant= number of capsules taken divided by the number of capsules prescribed as determined by pill count and described as a percentage per participant. Then the compliance of each participant in the assigned group (curcumin or placebo) was averaged together to obtain the medication compliance rate of that group.	Up to 12 months
Secondary	Change in Ornithine Decarboxylase (ODC) Activity Levels	Change in ODC mean activity levels (expressed as nmol of activity/mg of mucosal tissue/hr) at 8 months compared to baseline (time 0)	Baseline and 8 months
Secondary	Change in Total Polyamines Levels	Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline	Baseline and 8 months
Secondary	Change in Micro RNA 124-U6 (miR124-U6)	Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)	Baseline and 8 months
Secondary	Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)	Change in SSAT mean activity level at 8 months compared to baseline (time 0)	Baseline and 8 months
Secondary	Change in Spermine Oxidase (SMOX)	Change in SMOX mean activity level at 8 months compared to baseline (time 0)	Baseline and 8months
Secondary	Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels	Change in cellular proliferation rate was measured by assessment of Ki-67 anti-proliferative cell nuclear antibody index levels at 8 months	Baseline up to 8 months
Secondary	Change in Apoptosis Index Levels	Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement	8 months