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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 : Unknown
Verified February 2019 by Nicolas Musi, The University of Texas Health Science Center at San Antonio.
Recruitment status was:  Active, not recruiting
First Posted : April 28, 2014
Last Update Posted : February 7, 2019
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Nicolas Musi, The University of Texas Health Science Center at San Antonio

Tracking Information
First Submitted Date  ICMJE April 24, 2014
First Posted Date  ICMJE April 28, 2014
Last Update Posted Date February 7, 2019
Actual Study Start Date  ICMJE April 2, 2014
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
Insulin sensitivity [ Time Frame: At day 28th after put the intervention. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • Plasma endotoxin levels [ Time Frame: At baseline, on day 3, and 28 of the intervention. ]
  • Gut permeability [ Time Frame: on Day 24 of the intervention. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
Official Title  ICMJE Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Insulin Sensitivity
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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)
    Interventions:
    • Drug: Sevelamer
    • Drug: Synbiotic
    • Drug: Maltodextrin
  • 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)
    Interventions:
    • Drug: Sevelamer
    • Drug: Synbiotic
    • Drug: Maltodextrin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: February 6, 2019)
20
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2014)
36
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02124759
Other Study ID Numbers  ICMJE HSC20130459H
IRB #20130458H ( Other Grant/Funding Number: American Diabetes Association )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nicolas Musi, The University of Texas Health Science Center at San Antonio
Study Sponsor  ICMJE The University of Texas Health Science Center at San Antonio
Collaborators  ICMJE American Diabetes Association
Investigators  ICMJE
Principal Investigator: Nicolas Musi, MD. The University of Texas Health Science Center at San Antonio
PRS Account The University of Texas Health Science Center at San Antonio
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP