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Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2) (MicroB2)

This study is currently recruiting participants.
Verified April 2017 by Nicolas Musi, The University of Texas Health Science Center at San Antonio
Sponsor:
ClinicalTrials.gov Identifier:
NCT02127125
First Posted: April 30, 2014
Last Update Posted: April 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Nicolas Musi, The University of Texas Health Science Center at San Antonio
  Purpose
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.

Condition Intervention Phase
Insulin Sensitivity Drug: Maltodextrin Drug: Synbiotic Drug: Sevelamer Phase 2

Study Type: Interventional
Study Design: 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 (Aim2)

Resource links provided by NLM:


Further study details as provided by Nicolas Musi, The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: Change from baseline insulin sensitivity at 28 days of the intervention. ]

Secondary Outcome Measures:
  • Plasma endotoxin level and its panel. [ Time Frame: Change from baseline plasma endotoxin level and its panel during 28 days. ]
    Plasma Lipopolysaccharide (LPS), LPS binding protein (LBP), soluble cluster of differentiation (CD)14, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha.

  • Gut permeability [ Time Frame: Change from baseline gut permeability at 24 days of the intervention. ]
    urine for lactulose and mannitol ratio.


Estimated Enrollment: 108
Study Start Date: April 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Type2 Diabetes Mellitus

Type 2 Diabetes Mellitus (36 completers)

  • 12 subjects will receive the synbiotic
  • 12 subjects will receive sevelamer
  • 12 subjects will receive maltodextrin (placebo)
Drug: Maltodextrin
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Drug: Synbiotic
Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
Drug: Sevelamer
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Name: Renvela
Active Comparator: Obese with NGT

Obese (BMI = 30-37 kg/m2) normal glucose tolerant (36 completers)

  • 12 subjects will receive the synbiotic
  • 12 subjects will receive sevelamer
  • 12 subjects will receive maltodextrin (placebo)
Drug: Maltodextrin
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Drug: Synbiotic
Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
Drug: Sevelamer
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Name: Renvela
Active Comparator: Lean with NGT

Lean (BMI< 26 kg/m2) normal glucose tolerant (36 completers)

  • 12 subjects will receive the synbiotic
  • 12 subjects will receive sevelamer
  • 12 subjects will receive maltodextrin (placebo)
Drug: Maltodextrin
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Drug: Synbiotic
Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
Drug: Sevelamer
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Name: Renvela

Detailed Description:
In this Aim we will test the hypothesis that lowering lipopolysaccharide (LPS) concentration in the circulation will improve systemic (muscle) inflammation and glucose metabolism in insulin resistant (obese and T2DM) subjects by protecting the intestinal barrier with a synbiotic (Bifidobacterium longum R0175 and oligofructose) or by sequestering LPS in the gastrointestinal lumen with sevelamer.
  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

  • 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.

Exclusion 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.
  • 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.
  Contacts and Locations
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): NCT02127125


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    sathavarodom@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
  More Information

Responsible Party: Nicolas Musi, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02127125     History of Changes
Other Study ID Numbers: HSC20130458H
First Submitted: April 24, 2014
First Posted: April 30, 2014
Last Update Posted: April 17, 2017
Last Verified: April 2017

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