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Curcumin in Treating Patients With Familial Adenomatous Polyposis

Primary Purpose

Familial Adenomatous Polyposis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Curcumin
Laboratory Biomarker Analysis
Placebo
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Adenomatous Polyposis

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • University of Puerto Rico

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (curcumin)

Arm II (placebo)

Arm Description

Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis

Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mean Polyp Size in mm
Mean size of the 5 largest polyps
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.
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.
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.
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)
Change in Total Polyamines Levels
Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline
Change in Micro RNA 124-U6 (miR124-U6)
Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)
Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)
Change in SSAT mean activity level at 8 months compared to baseline (time 0)
Change in Spermine Oxidase (SMOX)
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
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
Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement

Full Information

First Posted
March 17, 2008
Last Updated
September 27, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00641147
Brief Title
Curcumin in Treating Patients With Familial Adenomatous Polyposis
Official Title
Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Adenomatous Polyposis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (curcumin)
Arm Type
Experimental
Arm Description
Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis
Intervention Type
Drug
Intervention Name(s)
Curcumin
Other Intervention Name(s)
C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric Yellow
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, sham therapy
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Polyp Number
Description
Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Mean Polyp Size in mm
Description
Mean size of the 5 largest polyps
Time Frame
Up to 12 months
Title
Number of Participants With a Decrease in Polyp Burden at 12 Months
Description
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.
Time Frame
12 months
Title
Number of Participants With Grade >=2 Adverse Events
Description
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.
Time Frame
Up to 12 months
Title
Medication Compliance
Description
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.
Time Frame
Up to 12 months
Title
Change in Ornithine Decarboxylase (ODC) Activity Levels
Description
Change in ODC mean activity levels (expressed as nmol of activity/mg of mucosal tissue/hr) at 8 months compared to baseline (time 0)
Time Frame
Baseline and 8 months
Title
Change in Total Polyamines Levels
Description
Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline
Time Frame
Baseline and 8 months
Title
Change in Micro RNA 124-U6 (miR124-U6)
Description
Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)
Time Frame
Baseline and 8 months
Title
Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)
Description
Change in SSAT mean activity level at 8 months compared to baseline (time 0)
Time Frame
Baseline and 8 months
Title
Change in Spermine Oxidase (SMOX)
Description
Change in SMOX mean activity level at 8 months compared to baseline (time 0)
Time Frame
Baseline and 8months
Title
Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels
Description
Change in cellular proliferation rate was measured by assessment of Ki-67 anti-proliferative cell nuclear antibody index levels at 8 months
Time Frame
Baseline up to 8 months
Title
Change in Apoptosis Index Levels
Description
Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement
Time Frame
8 months
Other Pre-specified Outcome Measures:
Title
Change in Mucosal DNA Methylation Levels.
Time Frame
Baseline to up to 12 months
Title
Change in Mucosal Leukotriene Levels.
Time Frame
Baseline to up to 12 months.
Title
Change in Mucosal Prostaglandin Levels.
Time Frame
Baseline to up to 12 months.
Title
Number of Patients Failing Study.
Description
Patients withdrawn from study due to increasing polyp burden and/or advancing histology.
Time Frame
Up to 16 months.
Title
Change in Vascular Density
Time Frame
Baseline up to 12 months
Title
Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway
Time Frame
Baseline to 12 months
Title
Change in Akt Phosphorylation Levels
Time Frame
Baseline up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francis Giardiello
Organizational Affiliation
Johns Hopkins University/Sidney Kimmel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Puerto Rico
City
San Juan
ZIP/Postal Code
00936
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29802852
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.
Results Reference
derived

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Curcumin in Treating Patients With Familial Adenomatous Polyposis

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