Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2) (MicroB2)

The University of Texas System (UT)

Status and phase: Completed; Phase 2

Conditions: Insulin Sensitivity

Treatments: Drug: Maltodextrin; Drug: Synbiotic; Drug: Sevelamer

Study type: Interventional

Funder types: Other

Identifiers

NCT02127125

HSC20130458H

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 69 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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69 participants in 9 patient groups, including a placebo group

Type2 Diabetes Mellitus - Placebo

Placebo Comparator group

Description:

Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)

Treatment:

Drug: Maltodextrin

Obese with NGT - Placebo

Placebo Comparator group

Description:

Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)

Treatment:

Drug: Maltodextrin

Lean with NGT -Placebo

Placebo Comparator group

Description:

Lean (BMI\< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)

Treatment:

Drug: Maltodextrin

Type2 Diabetes Mellitus - Synbiotic

Active Comparator group

Description:

Type 2 Diabetic subjects will receive synbiotic

Treatment:

Drug: Synbiotic

Type2 Diabetes Mellitus - Sevelamer

Active Comparator group

Description:

Type 2 Diabetic subjects will receive sevelamer

Treatment:

Drug: Sevelamer

Obese with NGT - Synbiotic

Active Comparator group

Description:

Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic

Treatment:

Drug: Synbiotic

Obese with NGT - Sevelamer

Active Comparator group

Description:

Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer

Treatment:

Drug: Sevelamer

Lean with NGT - Synbiotic

Active Comparator group

Description:

Lean (BMI\< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic

Treatment:

Drug: Synbiotic

Lean with NGT - Sevelamer

Active Comparator group

Description:

Lean (BMI\< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer

Treatment:

Drug: Sevelamer