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Blood Lipopolysaccharide (LPS) Rifaximin Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02124512
Recruitment Status : Recruiting
First Posted : April 28, 2014
Last Update Posted : March 14, 2019
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Philip Kern, University of Kentucky

Brief 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.

Condition or disease Intervention/treatment Phase
Obese Insulin Resistance Metabolic Syndrome Drug: Rifaximin SSD Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Dietary Fat, Lipoprotein and Lipopolysaccharide: Role in Insulin Resistance
Study Start Date : March 2015
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. 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:
  1. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 65 Years   (Adult, Older 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02124512

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

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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)
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Principal Investigator: Phililp Kern, MD University of Kentucky

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Responsible Party: Philip Kern, Sponsor-Investigator, University of Kentucky Identifier: NCT02124512     History of Changes
Other Study ID Numbers: 14-0136-F1V
UL1TR000117 ( U.S. NIH Grant/Contract )
1R21DK100258-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 28, 2014    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019

Keywords provided by Philip Kern, University of Kentucky:
insulin resistance
metabolic syndrome

Additional relevant MeSH terms:
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Metabolic Syndrome
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents