Role of Methane in Glycemic Control

NCT ID: NCT01638429

Last Updated: 2019-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-04-30

Brief Summary

The purpose of this study is to determine how certain types of bacteria in the human gut may affect weight gain, and contribute to the development of diabetes.

The investigators initial studies have shown that gut bacteria that produce methane may directly affect weight gain. These bacteria, called methanogens, produce methane gas as a byproduct, which can be detected through breath testing. Methane can slow the passage of food through the intestines, which would allow extra time for uptake and absorption of nutrients and calories, and might contribute to weight gain. The investigators have also found that people who have increased levels of methane-producing bacteria in their intestines also have higher levels of glucose in their blood. Therefore, control of how the body responds to insulin and uses glucose may be altered in methane-producing individuals.

This research study is designed to test the investigational use of the drugs neomycin and rifaximin that have been approved by the U.S Food and Drug Administration (FDA). While neomycin is FDA-approved for treating skin infections, preparing the bowel for surgery, and hepatic encephalopathy (a condition that occurs when a damaged liver cannot remove the toxins that a healthy liver normally would), and rifaximin is FDA-approved for treating travelers' diarrhea, they are not yet approved to be used together for the treatment of methanogens or obesity.

Detailed Description

Pre-diabetes is defined by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and affects more than 40% of US adults. While glycemic dysregulation and insulin resistance are central to the progression from pre-diabetes to diabetes, obesity also plays a key role. Research has begun to define the relationship between gut flora, metabolism and weight gain. Animal studies have linked a specific methanogen, Methanobrevibacter smithii, to weight gain, and in humans we have found that increased methane on breath test is associated both with increased body mass index (BMI) and higher blood glucose levels. We also found that methane gas directly slows gut transit by 59% in an in vivo animal model. We hypothesize that this slowing of transit could result in a greater time to harvest nutrients and absorb calories, representing a potential mechanism for elevated post-prandial glycemic excursions and weight gain. In this study, we will test this hypothesis by determining the effects of enteric methane production on glucose excursions, gut transit and energy utilization in obese or overweight, prediabetic, adult subjects.

We will explore the relationship between methane, M. smithii, obesity and gut transit in human subjects using objective measures of metabolic function, glucose excursions, energy utilization and transit studies, to evaluate whether intestinal methane production is associated with a higher incidence of diabetes risk in an obese study population. We will then repeat testing following a course of antibiotics known to eliminate methanogens. This will potentially provide novel therapies for the pre-diabetic patient, and allow new avenues for research.

Conditions

Diabetes; Obesity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Obese/overweight, prediabetic methane positive

Neomycin Rifaximin

Group Type: EXPERIMENTAL

Neomycin

Intervention Type: DRUG

Neomycin: 500mg po bid for 10 days

Rifaximin

Intervention Type: DRUG

Rifaximin: 550mg po tid for 10 days

Interventions

Neomycin

Neomycin: 500mg po bid for 10 days

Intervention Type: DRUG

Rifaximin

Rifaximin: 550mg po tid for 10 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18-65 years old with pre-diabetes (hemoglobin a1c of 5.7-6.4%)
• BMI > 25.0
• presence of methane on a breath sample (>3ppm)

Exclusion Criteria

Subjects will be excluded from the study if they exhibit any of the following:

• Diabetes/diabetes medications
• Prokinetic medication
• Pregnancy
• History of bariatric or intestinal surgery (other than cholecystectomy or appendectomy)
• Unstable thyroid disease
• An active weight loss treatment/plan
• Smoking
• Dietary restrictions (lactose intolerance, vegan etc)
• Other inability to comply with the study procedures, including known allergy to the study antibiotics (neomycin and rifaximin)
• Active inflammatory bowel disease (celiac, Crohn's disease, ulcerative colitis)
• Antibiotic use in the past month
• Subjects who do not have a microwave (for reheating study meals) and a freezer (for storing leftovers and stool samples) will be excluded from this study.
• Subjects who have an aspirin sensitivity
• Proton pump inhibitor medications or antacids
• History of bezoar
• Disorders of swallowing
• Suspected strictures, fistulas or physiological GI obstruction
• GI surgery within 3 months
• Severe dysphagia to food or pills
• Diverticulitis
• Subjects who use an implanted or portable electromechanical device such as a cardiac pacemaker or infusion pump
• Subject who have a peanut allergy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ruchi Mathur

Director, Clinical Diabetes Outpatient Treatment and Education Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ruchi Mathur, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

25182

Identifier Type: -

Identifier Source: org_study_id