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Trial record 2 of 2 for:    Musi | microbiome

Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1) (MicroB1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02124759
Recruitment Status : Completed
First Posted : April 28, 2014
Results First Posted : October 15, 2021
Last Update Posted : October 15, 2021
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

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)

Condition or disease Intervention/treatment Phase
Insulin Sensitivity Drug: Sevelamer Drug: Synbiotic Drug: Maltodextrin Other: High Fat diet Other: Low Fat diet Phase 2

Detailed Description:

We will test the hypothesis that a high fat diet given to lean, normal glucose tolerant subjects will impair insulin signaling and sensitivity and modify gut microbiome composition and enhance intestinal permeability, which will increase plasma LPS concentration, induce an inflammatory response in peripheral tissues (skeletal muscle). Also we will test the hypothesis that the inflammatory response and insulin resistance caused by high fat ingestion can be ameliorated by administering

  • a synbiotic (Bifidobacterium longum R0175 and oligofructose) which protects the intestinal epithelial barrier and decreases intestinal translocation of LPS; and
  • sevelamer, an agent which sequesters lipopolysaccharide (LPS) in the gastrointestinal tract limiting its translocation into the circulation.

All subjects are fed both a low fat diet (considered a normal diet) and high fat diet, first one and then the other in no particular sequence. After a washout period participants are fed the other type of high or low fat diet, depending on which diet they were first assigned to in order to compare the effects of the intervention on insulin sensitivity during each diet.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
Actual Study Start Date : April 2, 2014
Actual Primary Completion Date : February 23, 2018
Actual Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
Drug Information available for: Sevelamer

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo: maltodextrin, 6 g three times a day
Drug: Maltodextrin
This is a control group. Maltodextrin, 6 g three times a day

Other: 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.
Other Name: Isocaloric high fat diet

Other: Low Fat diet
The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.
Other Name: Isocaloric low fat (normal) diet

Active Comparator: Sevelamer
Sevelamer: (1.6 g sevelamer + 4.4 g maltodextrin three times a day)
Drug: Sevelamer
1.6 g sevelamer + 4.4 g maltodextrin three times a day
Other Name: Renvela

Other: 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.
Other Name: Isocaloric high fat diet

Other: Low Fat diet
The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.
Other Name: Isocaloric low fat (normal) diet

Active Comparator: Synbiotic
Synbiotic: 5g Oligofructose + 4x1010 Bifidobacterium longum CFU 3x daily during diet
Drug: Synbiotic
5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.

Other: 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.
Other Name: Isocaloric high fat diet

Other: Low Fat diet
The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.
Other Name: Isocaloric low fat (normal) diet




Primary Outcome Measures :
  1. Insulin Sensitivity Low Fat Diet [ Time Frame: Day 28 ]
    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.

  2. Insulin Sensitivity High Fat Diet [ Time Frame: Day 28 ]
    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.


Secondary Outcome Measures :
  1. Plasma Endotoxin Levels [ Time Frame: At baseline, on day 3, and 28 of the intervention. ]
    Endotoxin is a bacterially derived product that we hypothesized would impact insulin sensitivity through pro inflammatory pathways.

  2. Gut Permeability [ Time Frame: on Day 24 of the intervention. ]
    Gut permeability is measured using a lactulose/mannitol ingestion assay where urine samples are collected to analyse the ratio of excreted lactulose:mannitol.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02124759


Locations
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United States, Texas
Audie L. Murphy VA Hospital, STVHCS
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
American Diabetes Association
Investigators
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Principal Investigator: Nicolas Musi, MD. The University of Texas Health Science Center at San Antonio
  Study Documents (Full-Text)

Documents provided by The University of Texas Health Science Center at San Antonio:
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Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02124759    
Other Study ID Numbers: HSC20130459H
IRB #20130458H ( Other Grant/Funding Number: American Diabetes Association )
First Posted: April 28, 2014    Key Record Dates
Results First Posted: October 15, 2021
Last Update Posted: October 15, 2021
Last Verified: September 2021
Additional relevant MeSH terms:
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Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Sevelamer
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action