Clinical Trial: Curcumin in Preventing Gastric Cancer in Patients With Chronic Atrophic Gastritis or Gastric Intestinal Metaplasia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Randomized, Double-Blind, Placebo-Controlled Trial of Meriva® (Curcumin) as a Candidate Chemoprevention Agent for Gastric Carcinogenesis

Brief Summary: This randomized phase IIb trial studies how well curcumin works in preventing gastric cancer in patients with chronic atrophic gastritis and/or gastric intestinal metaplasia. Curcumin is an antioxidant compound found in plants that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the change in gastric mucosal interleukin (IL)-1beta cytokine level, quantified by Luminex assay technology, after a 6 month intervention in participants randomly assigned to the curcumin (Meriva) versus placebo arms.

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of Meriva versus placebo. II. To compare changes in Histology Gastric Score (HGS) from baseline to 6 months for Meriva versus placebo.

III. To compare changes in additional gastric mucosal cytokine/chemokine levels (IL-8, tumor necrosis factor-alpha [TNFalpha], and inducible protein[IP]-10; quantified by Luminex assay).

IV. To compare changes in gastric mucosal deoxyribonucleic acid (DNA) damage (gamma H2A histone family, member X [gamma-H2AX] assessed by flow cytometry).

V. To explore associations between proinflammatory cytokine genotype status (IL-1beta, IL-8, and TNFalpha single nucleotide polymorphisms [SNPs]; characterized at baseline) and the above outcomes.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM 1: Patients receive curcumin orally (PO) twice daily (BID) for 180 days in the absence of unacceptable toxicity.

ARM 2: Patients receive placebo PO BID for 180 days.

After completion of study treatment, patients are followed up at 30 days and 7 months.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Absolute change in IL-1beta cytokine levels in the gastric mucosa measured by Luminex assay [ Time Frame: Baseline up to 6 months ]

If the data are not normally distributed, the Wilcoxon Rank-Sum test will be used. The 95% confidence intervals will also be provided.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Additional gastric mucosal cytokine/chemokine levels (IL-8, TNFalpha, and IP-10), quantified with Luminex assay [ Time Frame: Baseline up to 6 months ]
    Changes in the concentrations (or categories) will be explored within and between the intervention arms. Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.
  • Change in histology gastric score [ Time Frame: Baseline up to 6 months ]
    Will compare changes in histology gastric score for curcumin versus placebo.
  • Gastric epithelial cell DNA damage, assessed by flow cytometry [ Time Frame: Baseline up to 6 months ]
    Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.
  • Incidence of adverse events graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: From time of first dose of curcumin up to 7 months ]
    The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events (overall and by intervention group) will be tabulated and summarized.


Original Secondary Outcome:

  • Additional gastric mucosal cytokine/chemokine levels (IL-8, TNFalpha, and IP-10), quantified with Luminex assay [ Time Frame: Baseline up to 6 months ]
    Changes in the concentrations (or categories) will be explored within and between the intervention arms. Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.
  • Change in HGS [ Time Frame: Baseline up to 6 months ]
    Will compare changes in HGS for curcumin versus placebo.
  • Gastric epithelial cell DNA damage, assessed by flow cytometry [ Time Frame: Baseline up to 6 months ]
    Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.
  • Incidence of adverse events graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: From time of first dose of curcumin up to 7 months ]
    The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events (overall and by intervention group) will be tabulated and summarized.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 25, 2016
Date Started: April 4, 2017
Date Completion: February 1, 2019
Last Updated: April 23, 2017
Last Verified: April 2017