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

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ClinicalTrials.gov Identifier: NCT02124759
Recruitment Status : Recruiting
First Posted : April 28, 2014
Last Update Posted : March 23, 2018
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Nicolas Musi, The University of Texas Health Science Center at San Antonio

Brief Summary:
The purpose of this study is to determine the effect of high fat consumption on the intestinal microbiome, metabolic endotoxemia, and insulin action, in lean normal glucose tolerant subjects.

Condition or disease Intervention/treatment Phase
Insulin Sensitivity Drug: Sevelamer Drug: Synbiotic Drug: Maltodextrin Phase 2

Detailed Description:

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
Study Start Date : April 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Sevelamer

Arm Intervention/treatment
Active Comparator: High fat diet

The high fat diet will provide 60% of energy from fat (of which 50% from saturated fat), 15% of energy as CHO and 25% from protein.

subjects will be randomized to receive, in a double-blind fashion

  • placebo, maltodextrin, 6 g three times a day
  • synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion CFU/g)three times a day]
  • 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

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

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

Active Comparator: Low fat diet

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

subjects will be randomized to receive, in a double-blind fashion

  • placebo, maltodextrin, 6 g three times a day
  • synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion CFU/g)three times a day]
  • 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

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

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




Primary Outcome Measures :
  1. Insulin sensitivity [ Time Frame: At day 28th after put the intervention. ]

Secondary Outcome Measures :
  1. Plasma endotoxin levels [ Time Frame: At baseline, on day 3, and 28 of the intervention. ]
  2. Gut permeability [ Time Frame: on Day 24 of the intervention. ]


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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


Contacts
Contact: Nicolas Musi, MD. 210-630-5001 Musi@uthscsa.edu
Contact: Lauri Che Kelly, RN. 210-617-5300 ext 14731 che@uthscsa.edu

Locations
United States, Texas
Audie L. Murphy VA Hospital, STVHCS Recruiting
San Antonio, Texas, United States, 78229
Contact: Nicolas Musi, MD.    210-617-5300 ext 15197    Musi@uthscsa.edu   
Contact: Lauri Che Kelly, RN    210-617-5300 ext 14731    che@uthscsa.edu   
Principal Investigator: Nicolas Musi, MD         
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
American Diabetes Association
Investigators
Principal Investigator: Nicolas Musi, MD. The University of Texas Health Science Center at San Antonio

Responsible Party: Nicolas Musi, Nicolas Musi, MD, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02124759     History of Changes
Other Study ID Numbers: HSC20130459H
IRB #20130458H ( Other Grant/Funding Number: American Diabetes Association )
First Posted: April 28, 2014    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Sevelamer
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action