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Completed

NCT Number: NCT02124512

Blood Lipopolysaccharide (LPS) Rifaximin Study

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.

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Key information

Conditions

Obese Body Weight Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Metabolic Syndrome Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

35 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Kentucky Center for Clinical and Translational Science

Lexington, Kentucky, 40536, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Rifaximin SSD

Drug

Study Drug dosing will be 80 mg SSD once daily

Placebo

Other

80 mg placebo once daily

Primary outcomes

  1. Circulating LPS

    Time frame: 0, 4 and 8 hours at Baseline, and 0, 4 and 8 hours after 12 weeks of treatment

    Plasma lipopolysaccharide (LPS) will be measured both in the fasting state and after a lipid-rich meal in obese subjects (Pre-Treatment: 0, 4 and 8 hr timepoints). The subjects will then be treated with the antibiotic rifaximin for 12 weeks to substantially reduce gut bacteria. LPS measurements at fasting and after a lipid-rich meal will be repeated (Post-Treatment: 0, 4 and 8 hr timepoints). The lipid tolerance tests before and after treatment with rifaximin will be assessed to determine whether there is a reduction in post-prandial LPS. LPS measurements were obtained using a modified LAL Assay.

Secondary outcomes

  1. Tissue Inflammation

    Time frame: Pre-Treatment (baseline) and Post-Treatment (12 weeks after baseline).

    Subjects will undergo a baseline fat biopsy (pre-treatment). They will then be treated with rifaximin for 12 weeks and biopsies will be repeated to determine if disruption of the microbiota reduces tissue inflammation. Data are reported as normalized mRNA expression levels (arbitrary units) of TNFalpha.

Other outcomes

  1. Improved Insulin Sensitivity

    Time frame: Up to 12 weeks

    We hypothesize that a change in the microbial flora with rifaximin will alter plasma LPS, adipose tissue inflammation, and 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).

Sponsors and collaborators

Lead sponsor

Philip Kern

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

Dietary Fat, Lipoprotein and Lipopolysaccharide: Role in Insulin Resistance

Important dates

Study start
2015
Primary completion
2019
Study completion
2019
First posted
Apr 28, 2014
Registry last updated
Aug 21, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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