Ginger and Gut Microbiome (GINGER)

Study Overview
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Brief Summary
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Estimate the impact of a 6-week daily intake of 2000 mg of ginger extract on the composition of the gut microbiome using a randomized placebo-controlled double-blinded design, i.e. examine the change of microbiome over time within and between the subjects..

Detailed Description
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This is a pilot trial to evaluate the feasibility of conducting a large randomized trial and estimate the effects of ginger extract on the gut microbiome. The pilot study will recruit from multiple sites 95-100 subjects aged 50-75 years old who were diagnosed with colorectal adenoma within the last five years. There will be 47-50 subjects in the treatment group and 47-50 in the placebo group. The subjects will be randomized to receive either 2000 mg of ginger extract per day (1000 mg twice a day) or matching placebo. Subjects will provide three stool specimens for analysis of the intestinal microbiome over a 12-week period at the following intervals: Week 0 (Day 1), Week 6, and Week 12. Although the gut microbiome is stable within a period of 1-2 months, a control arm will be included to account for potential dietary and other changes that may affect the gut microbiome. Gut microbiome composition - the presence, abundance, and diversity of bacterial taxa - will be derived by sequencing microbial 16S ribosomal RNA genes. Primary Aims: Aim 1 is to estimate the impact of a 6-week daily intake of 2000 mg of ginger extract on the composition of the gut microbiome using a randomized placebo-controlled double-blinded design, i.e. examine the change of microbiome over time within and between the subjects. Aim 2 will examine the correlation between the ginger-related changes in microbiome profile with the levels of circulating biomarkers: urinary Prostaglandin E (PGE) metabolites. Hypothesis: In the ginger versus placebo arm, gut microbiome will shift towards a lower proportion of pro-inflammatory, bacteria associated with colorectal cancer (CRC) and higher proportion of anti-inflammatory, CRC-protective bacteria. Secondary Aim: At the end of the study, we expect to show that ginger decreases the relative abundance of pro-inflammatory, CRC-predisposing taxa and increases the abundance of anti-inflammatory, CRC-protective taxa, i.e., demonstrate that ginger boosts changes in gut microbiome that are protective against CRC, as well as assess ginger-induced changes in immune response. The similarities of bacterial profiles will be compared between three time points baseline and 6 Weeks and 12 Weeks to estimate whether 6-week is a sufficient time for washout.

Official Title
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Pilot Trial to Examine the Effect of Ginger on the Gut Microbiome (GINGER)

Conditions
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Colorectal Adenoma

Intervention / Treatment
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* Dietary Supplement: Ginger extract
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Colorectal adenoma diagnosis Exclusion Criteria: Allergy or sensitivity to ginger Active cancer Unstable medical condition Unstable diet or weight

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot. Double-blind placebo-controlled randomized trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ginger extract<br>Ginger extract, 2000 mg daily for 6 weeks, followed by 6 week washout. | Dietary Supplement: Ginger extract<br>* 2000 mg ginger extract daily for 6 weeks, plus 6 weeks washout<br>|
| Experimental: Placebo<br>Placebo, daily for 6 weeks, followed by 6 week washout. | Other: Placebo<br>* 2000 mg ginger extract daily for 6 weeks, plus 6 weeks washout<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composition of the gut microbiome | Fecal microbial diversity and the prevalence of specific taxa associated with colorectal cancer (e.g. Fusobacteria, butyrate producing bacteria) will be estimated at 6 weeks. The ginger-related changes in the prevalence of each taxon will be assessed individually and also combined into a microbiome index (the abundance of protective taxa will be included as a negative value). | Baseline to 6 Weeks | 
| Urine inflammatory biomarker | Urinary metabolite of Prostaglandin E2 (ng/mg of creatinine) will be measured before and after treatment with ginger. Changes in inflammatory markers will be correlated to changes in the microbial diversity and the microbiome composition | Baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut microbiome composition | Beta-diversity will be compared between three time points: baseline, 6 Weeks and 12 Weeks. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gingerol, microbiome, gut, ginger