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Completed

NCT Number: NCT02127125

Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)

The purpose of this study is to determine whether microbiome modulation and an experimental reduction in plasma LPS concentration improve inflammation and insulin action in insulin resistant (obese and T2DM) subjects.

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Key information

Conditions

Insulin Sensitivity Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Audie L. Murphy VA Hospital, STVHCS

San Antonio, Texas, 78229, United States

About this study

In this Aim we will test the hypothesis that lowering lipopolysaccharide (LPS) concentration in the circulation will improve systemic (muscle) inflammation and glucose metabolism in insulin resistant (obese and T2DM) subjects by protecting the intestinal barrier with a synbiotic (Bifidobacterium longum R0175 and oligofructose) or by sequestering LPS in the gastrointestinal lumen with sevelamer.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Both genders (50%, male). All races and ethnic groups.
  • Premenopausal women in the follicular phase, non-lactating, and with a negative pregnancy test. Postmenopausal women on stable dose of or not exposed to hormone replacement for ≥6 months.
  • Hematocrit (HCT)≥ 34%, serum creatinine ≤ 1.4 mg/dl, and normal results of serum electrolytes, urinalysis, and coagulation tests. Liver function tests (LFTs) up to 2 times normal
  • Stable body weight (±2%) for ≥ 3 months.
  • Two or less sessions of strenuous exercise/wk for last 6 months.

Exclusion criteria

  • Current treatment with drugs known to affect glucose and lipid homeostasis. If the subject has been on a stable dose for the past 3 months, the following agents will be permitted: calcium channel blockers, β-blockers, ACE inhibitors, angiotensin receptor blockers, and statins
  • History of allergy to sevelamer.
  • Non-steroidal anti-inflammatory drugs or systemic steroid use for more than a week within 3 months.
  • Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsy in accordance with the primary physician.
  • Use of agents that affect gut flora (e.g. antibiotics, colestyramine, lactulose, PEG) within 3 months.
  • History of heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the ECG), peripheral vascular disease, pulmonary disease, smokers.
  • Poorly controlled blood pressure (systolic BP>170, diastolic BP>95 mmHg).
  • Active inflammatory, autoimmune, hepatic, gastrointestinal, malignant, and psychiatric disease.
  • History of gastrointestinal surgery or gastrointestinal obstruction within two years.

Treatment and study plan

Maltodextrin

Drug

Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.

Synbiotic

Drug

Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.

Sevelamer

Drug

Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks

Other names: Renvela

Primary outcomes

  1. Insulin Sensitivity

    Time frame: Change from baseline insulin sensitivity at 28 days of the intervention.

    Insulin sensitivity in skeletal muscle (M value) as measured by hyperinsulinemic euglycemic clamp study. The clamp study tests the ability of peripheral tissues such as skeletal muscle to uptake glucose in response to a constant insulin stimulus, which give a measure of sensitivity to insulin action. 60 mU/m2*min insulin was infused into subjects for 180 minutes with concomitant adjustment of glucose infusion rate using D20 glucose to maintain a clamped plasma glucose concentration of 100 mg/dL. When the glucose infusion rate equals the rate of glucose uptake and the targeted glucose concentration is achieved, the clamp is at steady-state equilibrium. Steady-state glucose infusion rate at 150min-180mins was used as the measure to calculate the M value.

Secondary outcomes

  1. Plasma Endotoxin Level and Its Panel.

    Time frame: Change from baseline plasma endotoxin level and its panel during 28 days.

    Plasma Lipopolysaccharide (LPS) after intervention period

  2. Gut Permeability

    Time frame: Change from baseline gut permeability at 24 days of the intervention.

    urine lactulose: mannitol ratio.

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center at San Antonio

Other

Collaborators

  • American Diabetes Association

Registry information

Acronym: MicroB2

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Apr 30, 2014
Registry last updated
Sep 11, 2020

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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