Blood Lipopolysaccharide (LPS) Rifaximin Study
Condition: Obese; Insulin Resistance; Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Insulin Resistance
Study type: Interventional
Phase: Phase 2

Summary: 
      Metabolic syndrome is a condition involving elevated levels of fat in the blood, a tendency
      towards diabetes, hypertension, and too much fat around the abdomen (an increased waistline).
      Individuals with metabolic syndrome often have impaired glucose tolerance, which is a
      condition where blood sugar is normal when fasting (before eating), but is too high after
      drinking a sugary drink. This is due to an abnormality in the body's sensitivity to insulin
      (insulin resistance), which is due in part to an inability of the muscle to take up glucose.

      People with metabolic syndrome have inflammation in their fat tissue and in their blood
      stream, and the changes in the level of inflammatory chemicals produced by cells in your fat
      tissues will be studied. One possible source of the inflammation may be the bacteria in the
      intestine. When individuals eat fatty foods, some of the bacterial products become attached
      to the fat in their blood and then get directed to fat tissue. The investigators wish to
      determine whether individuals have an excessive amount of inflammation in their fat tissues,
      and whether this inflammation comes from the bacteria in their intestines. To determine this,
      the investigators wish to treat individuals with an antibiotic that reduces the bacteria in
      their intestines and in their blood, and determine whether this reduces their overall level
      of inflammation.
    

Detailed description: 
      This is a randomized, placebo-controlled proof of concept study that will examine the
      investigational drug Rifaximin Soluble Solid Dispersion (SSD) ability to reduce gut
      microbiota and thereby reduce adipose inflammation and improve insulin resistance.

      Each subject enrolled will undergo a fat tolerance test with a high-fat meal, an oral glucose
      tolerance test, a fat biopsy, and a euglycemic clamp. Following their successful completion
      of those procedures subjects will be randomized to study treatment. That treatment will
      involve receiving the investigational drug,80 mg per day of rifaximin-soluble solid
      dispersion (SDD), or placebo for 12 weeks. All procedures will be performed on the Clinical
      Services Core of the CCTS. The initial visit will involve informed consent, and routine labs
      (comprehensive metabolic panel, lipid panel, TSH, CBC with platelets). These routine labs are
      for safety purposes and to rule out exclusionary disorders. A stool sample will also be
      collected and frozen for possible future analysis of bacterial microflora.

      Subjects will be asked to allow the principal investigator to bank blood and tissue samples
      collected during this study that are not used for other study-related tests. No additional
      blood or tissue samples will be collected. If the subject agrees to the banking of their
      blood and tissue samples they will be stored in the Principal Investigator's laboratory at
      the University of Kentucky for an indefinite period of time or until they are used up. Stored
      samples will be used for future research testing to learn about how to prevent, detect, or
      treat insulin resistance, metabolic syndrome, diabetes or other health problems.

      Each subject will undergo total body composition testing using a total body dual-energy x-ray
      absorptiometry (DXA) scan. The DXA scan measures the subject's bond density and body fat.
    

Intervention name(s): Rifaximin SSD; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Study Drug dosing will be 80 mg SSD once daily; 80 mg placebo once daily
Intervention MeSH terms: Rifaximin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: obese; insulin resistance; metabolic syndrome