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Blood Lipopolysaccharide (LPS) Rifaximin Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University of Kentucky
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Philip Kern, University of Kentucky Identifier:
First received: April 23, 2014
Last updated: August 22, 2016
Last verified: August 2016

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.

Condition Intervention Phase
Insulin Resistance
Metabolic Syndrome
Drug: Rifaximin SSD
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Dietary Fat, Lipoprotein and Lipopolysaccharide: Role in Insulin Resistance

Resource links provided by NLM:

Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Decrease in circulating LPS [ Time Frame: up to 24 months ]
    We will measure plasma lipopolysaccharide (LPS) both in the fasting state and after a lipid-rich meal in obese MetS subjects. The subjects will then be treated with the antibiotic rifaximin for 8 weeks to substantially reduce gut bacteria. The lipid tolerance tests before and after treatment with rifaximin will be assessed to determine whether there is a reduction in post-prandial LPS.

Secondary Outcome Measures:
  • Decrease in tissue inflammation [ Time Frame: Up to 24 months ]
    Subjects will undergo a baseline fat biopsy and a euglycemic clamp to measure peripheral and hepatic insulin sensitivity. They will then be treated with rifaximin and the insulin sensitivity testing and biopsies will be repeated to determine if disruption of the microbiota reduces tissue inflammation and improves insulin sensitivity.

Other Outcome Measures:
  • Improved insulin sensitivity [ Time Frame: Up to 24 months ]
    We hypothesize that a change in the microbial flora with rifaximin will reduce plasma LPS, and this in turn will reduce adipose tissue inflammation, which may lead to improved insulin sensitivity. Therefore, we will examine, before and after rifaximin/placebo treatment: 1. LPS associated with lipoproteins, 2. insulin sensitivity and hepatic glucose production, 3. plasma inflammatory markers (TNFα, IL-6, MCP-1, adiponectin), 4. adipose inflammatory markers (CD68, MCP1, TNFα, PAI1, IL12, IL10, TLR4 and others).

Estimated Enrollment: 40
Study Start Date: March 2015
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Rifaximin SSD
Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD
Drug: Rifaximin SSD
Study Drug dosing will be 80 mg SSD once daily
Placebo Comparator: Arm 2 Placebo
Other: Placebo
80 mg placebo once daily

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 soluable solid dispersion (SDD), or placebo for 8 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.


Ages Eligible for Study:   35 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Obese
  • Insulin resistance or metabolic syndrome
  • Body Mass Index between 27 and 45
  • Waist circumference >40" (M) or >35" (F)
  • Impaired glucose tolerance (IGT)
  • Normal glucose tolerance (NGT) with at least three features of MetS
  • A1C <6.5
  • Blood pressure 130/85

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Recent or unstable cardiovascular disease
  • cancer,
  • Renal insufficiency (GFR<30)
  • Steroid use
  • chronic inflammatory conditions
  • Anticoagulant use
  • Lipodystrophy
  • Irritable Bowel Syndrome
  • Allergy to local anesthetic
  • Lactose intolerance
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02124512

Contact: Dorothy Ross (859) 323-2737
Contact: Philip Kern, MD (859) 323-4933

United States, Kentucky
University of Kentucky Center for Clinical and Translational Science Recruiting
Lexington, Kentucky, United States, 40536
Contact: Stacie BeBout    859-323-9987   
Principal Investigator: Philip Kern, MD         
Sponsors and Collaborators
Philip Kern
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Phililp Kern, MD University of Kentucky
  More Information

Responsible Party: Philip Kern, Sponsor-Investigator, University of Kentucky Identifier: NCT02124512     History of Changes
Other Study ID Numbers: 14-0136-F1V
UL1TR000117 ( US NIH Grant/Contract Award Number )
1R21DK100258-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: April 23, 2014
Last Updated: August 22, 2016

Keywords provided by University of Kentucky:
insulin resistance
metabolic syndrome

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Anti-Infective Agents
Gastrointestinal Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents processed this record on March 30, 2017