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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by University of California, Irvine.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Gateway for Cancer Research
Information provided by:
University of California, Irvine
ClinicalTrials.gov Identifier:
NCT00578396
First received: December 18, 2007
Last updated: May 4, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Dietary Supplement: grapes
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Biomarker Study of Dietary Grape-Derived Low Dose Resveratrol for Colon Cancer Prevention

Resource links provided by NLM:


Further study details as provided by University of California, Irvine:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2008
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dose Level 1
1 lb/day fresh red grapes
Dietary Supplement: grapes
1 pound of seedless red grapes
Other Name: dietary
Active Comparator: Dose Level 2
2/3 lb/day fresh red grapes
Dietary Supplement: grapes
2/3 lb/day fresh red grapes
Other Name: dietary
Active Comparator: Dose Level 3
1/3 lb/day fresh red grapes
Dietary Supplement: grapes
1/3 lb/day fresh red grapes
Other Name: dietary

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578396

Locations
United States, California
University of California, Irvine Medical Center
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
Gateway for Cancer Research
Investigators
Principal Investigator: Randall F Holcombe, M.D. University of California, Irvine
  More Information

No publications provided

Responsible Party: Randall F. Holcombe, M.D., University of California, Irvine
ClinicalTrials.gov Identifier: NCT00578396     History of Changes
Other Study ID Numbers: OCRT07046, Foundation grant
Study First Received: December 18, 2007
Last Updated: May 4, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Irvine:
Grapes and colon cancer prevention

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Resveratrol
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Hematologic Agents

ClinicalTrials.gov processed this record on September 18, 2014