Clinical trial NCT01638429
Conditions: Diabetes Obesity
Sponsor: Cedars-Sinai Medical Center
Start date: 2012-04-01; Completion date: 2014-04-01
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Neomycin Rifaximin
Interventions: intervention 1: Neomycin intervention 2: Rifaximin
Intervention descriptions: intervention 1: Neomycin: 500mg po bid for 10 days intervention 2: Rifaximin: 550mg po tid for 10 days

Protocol documents: