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

NCT02127125 | Completed Phase 2 Results DMC

• 1 other identifier: HSC20130458H
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Sensitivity

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity

  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.

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

Secondary Outcomes (2)

• Plasma Endotoxin Level and Its Panel.

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

• Gut Permeability

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

Study Arms (9)

Type2 Diabetes Mellitus - Placebo

PLACEBO COMPARATOR

Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)

Drug: Maltodextrin

Obese with NGT - Placebo

PLACEBO COMPARATOR

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

Drug: Maltodextrin

Lean with NGT -Placebo

PLACEBO COMPARATOR

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

Drug: Maltodextrin

Type2 Diabetes Mellitus - Synbiotic

ACTIVE COMPARATOR

Type 2 Diabetic subjects will receive synbiotic

Drug: Synbiotic

Type2 Diabetes Mellitus - Sevelamer

ACTIVE COMPARATOR

Type 2 Diabetic subjects will receive sevelamer

Drug: Sevelamer

Obese with NGT - Synbiotic

ACTIVE COMPARATOR

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

Drug: Synbiotic

Obese with NGT - Sevelamer

ACTIVE COMPARATOR

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

Drug: Sevelamer

Lean with NGT - Synbiotic

ACTIVE COMPARATOR

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

Drug: Synbiotic

Lean with NGT - Sevelamer

ACTIVE COMPARATOR

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

Drug: Sevelamer

Interventions

Maltodextrin DRUG

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

Lean with NGT -Placebo; Obese with NGT - Placebo; Type2 Diabetes Mellitus - Placebo

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.

Lean with NGT - Synbiotic; Obese with NGT - Synbiotic; Type2 Diabetes Mellitus - Synbiotic

Sevelamer DRUG

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

Also known as: Renvela

Lean with NGT - Sevelamer; Obese with NGT - Sevelamer; Type2 Diabetes Mellitus - Sevelamer

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• American Diabetes Association: collaborator

Study Sites (1)

Audie L. Murphy VA Hospital, STVHCS

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

maltodextrin; Synbiotics; Sevelamer

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Prebiotics; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Probiotics; Food and Beverages; Polyamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Nicolas Musi
• Organization: San Antonio Geriatric Research, Education, and Clinical Center

musi@uthscsa.edu

(210) 562-6140

Study Officials

• Nicolas Musi, MD.

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2014
• First Posted: April 30, 2014
• Study Start: April 10, 2014
• Primary Completion: September 1, 2018
• Study Completion: September 10, 2018
• Last Updated: September 11, 2020
• Results First Posted: September 11, 2020

Record last verified: 2020-08

Locations

US (1)