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Curcumin in Treating Patients With Familial Adenomatous Polyposis

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ClinicalTrials.gov Identifier: NCT00641147
Recruitment Status : Completed
First Posted : March 24, 2008
Results First Posted : September 29, 2017
Last Update Posted : September 29, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 17, 2008
First Posted Date  ICMJE March 24, 2008
Results First Submitted Date  ICMJE July 13, 2017
Results First Posted Date  ICMJE September 29, 2017
Last Update Posted Date September 29, 2017
Study Start Date  ICMJE October 2010
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
Polyp Number [ Time Frame: Up to 12 months ]
Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2008)
polyp number and size [ Time Frame: 1 year ]
Change History Complete list of historical versions of study NCT00641147 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
  • Mean Polyp Size in mm [ Time Frame: Up to 12 months ]
    Mean size of the 5 largest polyps
  • Number of Participants With a Decrease in Polyp Burden at 12 Months [ Time Frame: 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.
  • Number of Participants With Grade >=2 Adverse Events [ Time Frame: Up to 12 months ]
    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.
  • Medication Compliance [ Time Frame: Up to 12 months ]
    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.
  • Change in Ornithine Decarboxylase (ODC) Activity Levels [ Time Frame: Baseline and 8 months ]
    Change in ODC mean activity levels (expressed as nmol of activity/mg of mucosal tissue/hr) at 8 months compared to baseline (time 0)
  • Change in Total Polyamines Levels [ Time Frame: Baseline and 8 months ]
    Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline
  • Change in Micro RNA 124-U6 (miR124-U6) [ Time Frame: Baseline and 8 months ]
    Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)
  • Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT) [ Time Frame: Baseline and 8 months ]
    Change in SSAT mean activity level at 8 months compared to baseline (time 0)
  • Change in Spermine Oxidase (SMOX) [ Time Frame: Baseline and 8months ]
    Change in SMOX mean activity level at 8 months compared to baseline (time 0)
  • Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels [ Time Frame: Baseline up to 8 months ]
    Change in cellular proliferation rate was measured by assessment of Ki-67 anti-proliferative cell nuclear antibody index levels at 8 months
  • Change in Apoptosis Index Levels [ Time Frame: 8 months ]
    Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2008)
side effects and medication compliance [ Time Frame: 1 year ]
Current Other Pre-specified Outcome Measures
 (submitted: September 27, 2017)
  • Change in Mucosal DNA Methylation Levels. [ Time Frame: Baseline to up to 12 months ]
  • Change in Mucosal Leukotriene Levels. [ Time Frame: Baseline to up to 12 months. ]
  • Change in Mucosal Prostaglandin Levels. [ Time Frame: Baseline to up to 12 months. ]
  • Number of Patients Failing Study. [ Time Frame: Up to 16 months. ]
    Patients withdrawn from study due to increasing polyp burden and/or advancing histology.
  • Change in Vascular Density [ Time Frame: Baseline up to 12 months ]
  • Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway [ Time Frame: Baseline to 12 months ]
  • Change in Akt Phosphorylation Levels [ Time Frame: Baseline up to 12 months ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Curcumin in Treating Patients With Familial Adenomatous Polyposis
Official Title  ICMJE Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Familial Adenomatous Polyposis
Intervention  ICMJE
  • Drug: Curcumin
    Given PO
    Other Names:
    • C.I. 75300
    • C.I. Natural Yellow 3
    • Diferuloylmethane
    • Turmeric Yellow
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Placebo
    Given PO
    Other Names:
    • placebo therapy
    • sham therapy
Study Arms  ICMJE
  • Experimental: Arm I (curcumin)
    Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis
    Interventions:
    • Drug: Curcumin
    • Other: Laboratory Biomarker Analysis
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Other: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2017)
44
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2008)
50
Actual Study Completion Date  ICMJE November 30, 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00641147
Other Study ID Numbers  ICMJE NCI-2013-00536
NCI-2013-00536 ( Other Identifier: NCI )
CDR0000592794 ( Other Identifier: Clinical Trial Reporting Program )
NA_00011821 ( Other Identifier: Johns Hopkins University IRB )
1R01CA134620 ( U.S. NIH Grant/Contract )
R01CA134620 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Francis Giardiello Johns Hopkins University/Sidney Kimmel Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP