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

NCT ID: NCT02127125

Last Updated: 2020-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-10
• Study Completion Date: 2018-09-10

Brief Summary

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.

Detailed 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.

Conditions

Insulin Sensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Type2 Diabetes Mellitus - Placebo

Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: DRUG

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

Obese with NGT - Placebo

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

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: DRUG

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

Lean with NGT -Placebo

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

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: DRUG

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

Type2 Diabetes Mellitus - Synbiotic

Type 2 Diabetic subjects will receive synbiotic

Group Type: ACTIVE_COMPARATOR

Synbiotic

Intervention Type: 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.

Type2 Diabetes Mellitus - Sevelamer

Type 2 Diabetic subjects will receive sevelamer

Group Type: ACTIVE_COMPARATOR

Sevelamer

Intervention Type: DRUG

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

Obese with NGT - Synbiotic

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

Group Type: ACTIVE_COMPARATOR

Synbiotic

Intervention Type: 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.

Obese with NGT - Sevelamer

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

Group Type: ACTIVE_COMPARATOR

Sevelamer

Intervention Type: DRUG

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

Lean with NGT - Synbiotic

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

Group Type: ACTIVE_COMPARATOR

Synbiotic

Intervention Type: 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.

Lean with NGT - Sevelamer

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

Group Type: ACTIVE_COMPARATOR

Sevelamer

Intervention Type: DRUG

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

Interventions

Maltodextrin

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

Intervention Type: DRUG

Synbiotic

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

Intervention Type: DRUG

Sevelamer

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

Intervention Type: DRUG

Other Intervention Names

Renvela

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicolas Musi, MD.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Locations

Audie L. Murphy VA Hospital, STVHCS

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HSC20130458H

Identifier Type: -

Identifier Source: org_study_id