Role of Methane in Glycemic Control
Condition: Diabetes; Obesity
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Neomycin; Rifaximin
Intervention type(s): Drug; Drug
Intervention description(s): Neomycin: 500mg po bid for 10 days; Rifaximin: 550mg po tid for 10 days
Intervention MeSH terms: Rifaximin; Neomycin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment