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Phase I Biomarker Study of Dietary Grape-Derived Low Dose Resveratrol for Colon Cancer Prevention

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ClinicalTrials.gov Identifier: NCT00578396
Recruitment Status : Unknown
Verified May 2009 by University of California, Irvine.
Recruitment status was:  Active, not recruiting
First Posted : December 21, 2007
Last Update Posted : May 5, 2009
Sponsor:
Collaborator:
Gateway for Cancer Research
Information provided by:
University of California, Irvine

Tracking Information
First Submitted Date  ICMJE December 18, 2007
First Posted Date  ICMJE December 21, 2007
Last Update Posted Date May 5, 2009
Study Start Date  ICMJE January 2008
Estimated Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2007)
Expression and cellular localization of beta-catenin in intestinal mucosa: localization of β-catenin. Expression of Wnt pathway target genes in intestinal mucosa: Wnt target gene expression [ Time Frame: 2 yrs ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00578396 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2008)
  • Define whether grape supplemented diet affects colonic mucosa cell proliferation. Ki67 staining method will be utilized on the pre- and post-resveratrol biopsy specimens. [ Time Frame: 2 yrs ]
  • Define any side-effects associated with the resveratrol-rich dietary program. Laboratory testing is performed at specified timepoints in this protocol, along with history & physical, for the purposes of toxicity monitoring. [ Time Frame: 2 yrs ]
  • Monitor resveratrol content of grapes throughout the course of the study. Grapes will be obtained from the same source as participants monthly throughout the study and the content of resveratrol will be measured. [ Time Frame: 2 yrs ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2007)
  • Define whether grape supplemented diet affects colonic mucosa cell proliferation. PCNA staining method will be utilized on the pre- and post-resveratrol biopsy specimens. [ Time Frame: 2 yrs ]
  • Define any side-effects associated with the resveratrol-rich dietary program. Laboratory testing is performed at specified timepoints in this protocol, along with history & physical, for the purposes of toxicity monitoring. [ Time Frame: 2 yrs ]
  • Monitor resveratrol content of grapes throughout the course of the study. Grapes will be obtained from the same source as participants monthly throughout the study and the content of resveratrol will be measured. [ Time Frame: 2 yrs ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Biomarker Study of Dietary Grape-Derived Low Dose Resveratrol for Colon Cancer Prevention
Official Title  ICMJE Phase I Biomarker Study of Dietary Grape-Derived Low Dose Resveratrol for Colon Cancer Prevention
Brief Summary This study is designed to investigate the dietary influence of grapes in colon cancer prevention. A natural compound found in the skin of grapes, resveratrol, may protect against cancer by acting as an antioxidant (a chemical compound or substance that helps reduce damages due to oxygen). This compound is known to block colon cancer cell lines from growing in the laboratory. The purpose of this study is to determine the minimum amount of resveratrol-rich fresh red grapes needed to exhibit such signs of prevention.
Detailed Description

It has long been recognized that dietary factors influence the risk of developing colon cancer, with populations consuming a higher proportion of fruits and vegetables having lower risk. A compound found in the skin of grapes, resveratrol, has been purported to have colon cancer prevention activity though the dosages obtained through the diet have always seemed too low to produce inhibitory effects against cancer cells in the laboratory. We have found that low concentrations of resveratrol inhibit the Wnt pathway, a key signaling pathway which is activated in over 85% of colon cancers. We have also found in a small pilot trial that low dosages of freeze-dried grape powder can directly inhibit Wnt signaling in the normal colon and that grape powder was more effective than resveratrol alone in blocking Wnt throughput. This suggests that components of grapes may have direct activity in inhibiting a key signaling pathway and that this may correlate with cancer prevention activity.

In this study, we will directly test the impact of a diet containing a specific amount of red grapes in the context of a controlled amount of other resveratrol containing foodstuffs on Wnt signaling in the colon. This grape-supplemented diet provides a low-dose of resveratrol in conjunction with other potentially active components contained within the grapes. Participants will be normal volunteers and molecular studies will be done on colon tissue obtained by a limited flexible sigmoidoscopy before, and after, the red grape-containing diet is ingested. Different dosages of grapes will be utilized. This study will define the effect of dietary grape-derived low dose resveratrol on biomarkers related to the Wnt pathway, and provide critical information as to the utility of this nutritional approach toward colon cancer prevention.

For this study, seedless red grapes will be used. Ten participants will be enrolled at each dose level of grapes as follows:

  • Dose level 1: 1 lb/day fresh red grapes
  • Dose level 2: 2/3 lb/day fresh red grapes
  • Dose level 3: 1/3 lb/day fresh red grapes

Participants will be normal volunteers identified through advertisements, referrals, and community outreach.

Primary Objective:

Define the minimum dietarily achievable amount of resveratrol-rich fresh red grapes which are effective in inhibiting Wnt signaling in human colonic mucosa.

Secondary Objectives

  1. Define whether grape-supplemented diet affects colonic mucosa cell proliferation.
  2. Define any side-effects associated with the resveratrol-rich dietary program.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Colon Cancer
Intervention  ICMJE
  • Dietary Supplement: grapes
    1 pound of seedless red grapes
    Other Name: dietary
  • Dietary Supplement: grapes
    2/3 lb/day fresh red grapes
    Other Name: dietary
  • Dietary Supplement: grapes
    1/3 lb/day fresh red grapes
    Other Name: dietary
Study Arms  ICMJE
  • Active Comparator: Dose Level 1
    1 lb/day fresh red grapes
    Intervention: Dietary Supplement: grapes
  • Active Comparator: Dose Level 2
    2/3 lb/day fresh red grapes
    Intervention: Dietary Supplement: grapes
  • Active Comparator: Dose Level 3
    1/3 lb/day fresh red grapes
    Intervention: Dietary Supplement: grapes
Publications * Not Provided

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: December 18, 2007)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2010
Estimated Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 years of age or older, male or female
  • Participants must sign informed consent for enrollment
  • Participants must have values for tests included in CBC, CMPAN and UA within normal range or no greater than 1.5x ULN or less than 0.75x LLN at prestudy to proceed to registration
  • Participants must have normal limited flexible sigmoidoscopic examination on Day 15 to proceed to re-registration
  • To receive Day 28 limited flexible sigmoidoscopy, participants must have taken >80% of prescribed dose of red grapes (based on food diary review)

Exclusion Criteria:

  • Pregnant or lactating (and/or elevated ßHCG at enrollment)
  • Known history of diabetes
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00578396
Other Study ID Numbers  ICMJE OCRT07046
Foundation grant
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Randall F. Holcombe, M.D., University of California, Irvine
Study Sponsor  ICMJE University of California, Irvine
Collaborators  ICMJE Gateway for Cancer Research
Investigators  ICMJE
Principal Investigator: Randall F Holcombe, M.D. University of California, Irvine
PRS Account University of California, Irvine
Verification Date May 2009

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