Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)

NCT02124759 | Completed Phase 2 Results DMC

• 2 other identifiers: HSC20130459HIRB #20130458H
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine insulin sensitivity in individuals that are lean normal glucose tolerant subjects after consumption of a normal low fat diet and after a high fat diet and to explore the effects of high fat consumption on the intestinal microbiome, and metabolic endotoxemia.( Aim 1 of the protocol, a separate record is available for Aim 2)

Conditions

Insulin Sensitivity

Outcome Measures

Primary Outcomes (2)

• Insulin Sensitivity Low Fat Diet

  Skeletal muscle insulin sensitivity measured after 28 days of low fat diet and drug intervention. The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.

  Day 28

• Insulin Sensitivity High Fat Diet

  Skeletal muscle insulin sensitivity measured after 28 days of high fat diet. The High Fat diet consists of 60% energy from fat (50% saturated), 15% of energy as carbohydrate and 25% from protein consumed while study intervention is being administered.

  Day 28

Secondary Outcomes (2)

• Plasma Endotoxin Levels

  At baseline, on day 3, and 28 of the intervention.

• Gut Permeability

  on Day 24 of the intervention.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo: maltodextrin, 6 g three times a day

Drug: Maltodextrin; Other: High Fat diet; Other: Low Fat diet

Sevelamer

ACTIVE COMPARATOR

Sevelamer: (1.6 g sevelamer + 4.4 g maltodextrin three times a day)

Drug: Sevelamer; Other: High Fat diet; Other: Low Fat diet

Synbiotic

ACTIVE COMPARATOR

Synbiotic: 5g Oligofructose + 4x1010 Bifidobacterium longum CFU 3x daily during diet

Drug: Synbiotic; Other: High Fat diet; Other: Low Fat diet

Interventions

Sevelamer DRUG

1.6 g sevelamer + 4.4 g maltodextrin three times a day

Also known as: Renvela

Sevelamer

Synbiotic DRUG

5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.

Synbiotic

Maltodextrin DRUG

This is a control group. Maltodextrin, 6 g three times a day

Placebo

High Fat diet OTHER

The High Fat diet consists of 60% energy from fat (50% saturated), 15% of energy as carbohydrate and 25% from protein consumed while study intervention is being administered.

Also known as: Isocaloric high fat diet

Placebo; Sevelamer; Synbiotic

Low Fat diet OTHER

The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.

Also known as: Isocaloric low fat (normal) diet

Placebo; Sevelamer; Synbiotic

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. 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 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:

• Presence of diabetes or impaired glucose tolerance based on ADA 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.
• History of 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

Sevelamer; Synbiotics; maltodextrin; Diet, High-Fat; Diet, Fat-Restricted; Diet

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Despite continued recruitment efforts, we had difficulty with subjects fully completing the study due to dissatisfaction with the diets. Evaluable subjects completed both low and high fat diet while randomized to one of the three interventions, and only insulin sensitivity was captured for both the low fat and high fat diets due to the low completion numbers.

Results Point of Contact

• Title: Dr. Nicolas Musi
• Organization: UTHSC San Antonio

musi@uthscsa.edu

630-5001

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 28, 2014
• Study Start: April 2, 2014
• Primary Completion: February 23, 2018
• Study Completion: March 30, 2020
• Last Updated: October 15, 2021
• Results First Posted: October 15, 2021

Record last verified: 2021-09

Locations

US (1)