Blood Lipopolysaccharide (LPS) Rifaximin Study

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by University of Kentucky
Sponsor:
Information provided by (Responsible Party):
Philip Kern, University of Kentucky
ClinicalTrials.gov Identifier:
NCT02124512
First received: April 23, 2014
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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: June 2014
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
Placebo
Other: Placebo
80 mg placebo once daily
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT02124512

Contacts
Contact: Stacie BeBout (859) 323-9987 staciebebout@uky.edu
Contact: Philip Kern, MD (859) 323-4933 philipkern@uky.edu

Locations
United States, Kentucky
University of Kentucky Center for Clinical and Translational Science Not yet recruiting
Lexington, Kentucky, United States, 40536
Contact: Stacie BeBout    859-323-9987    stacybebout@uky.edu   
Principal Investigator: Philip Kern, MD         
Sponsors and Collaborators
Philip Kern
Investigators
Principal Investigator: Phililp Kern, MD University of Kentucky
  More Information

No publications provided

Responsible Party: Philip Kern, Sponsor-Investigator, University of Kentucky
ClinicalTrials.gov Identifier: NCT02124512     History of Changes
Other Study ID Numbers: 14-0136-F1V, UL1TR000117
Study First Received: April 23, 2014
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Kentucky:
obese
insulin resistance
metabolic syndrome

Additional relevant MeSH terms:
Insulin Resistance
Metabolic Syndrome X
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Silver Sulfadiazine
Rifaximin
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 26, 2014