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

Phase 1
18 Years
Open (Enrolling)
Colon Cancer

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Trial Information

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

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.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

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

Outcome Time Frame:

2 yrs

Safety Issue:


Principal Investigator

Randall F Holcombe, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Irvine


United States: Institutional Review Board

Study ID:




Start Date:

January 2008

Completion Date:

January 2010

Related Keywords:

  • Colon Cancer
  • Grapes and colon cancer prevention
  • Colonic Neoplasms



University of California, Irvine Medical Center Orange, California  92868