Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT02127125
Recruitment Status : Completed
First Posted : April 30, 2014
Results First Posted : September 11, 2020
Last Update Posted : September 11, 2020
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Tracking Information
First Submitted Date  ICMJE April 24, 2014
First Posted Date  ICMJE April 30, 2014
Results First Submitted Date  ICMJE August 3, 2020
Results First Posted Date  ICMJE September 11, 2020
Last Update Posted Date September 11, 2020
Actual Study Start Date  ICMJE April 10, 2014
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
Insulin Sensitivity [ Time Frame: Change from baseline insulin sensitivity at 28 days of the intervention. ]
Insulin sensitivity in skeletal muscle (M value) as measured by hyperinsulinemic euglycemic clamp study. The clamp study tests the ability of peripheral tissues such as skeletal muscle to uptake glucose in response to a constant insulin stimulus, which give a measure of sensitivity to insulin action. 60 mU/m2*min insulin was infused into subjects for 180 minutes with concomitant adjustment of glucose infusion rate using D20 glucose to maintain a clamped plasma glucose concentration of 100 mg/dL. When the glucose infusion rate equals the rate of glucose uptake and the targeted glucose concentration is achieved, the clamp is at steady-state equilibrium. Steady-state glucose infusion rate at 150min-180mins was used as the measure to calculate the M value.
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2014)
Insulin Sensitivity [ Time Frame: Change from baseline insulin sensitivity at 28 days of the intervention. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
  • Plasma Endotoxin Level and Its Panel. [ Time Frame: Change from baseline plasma endotoxin level and its panel during 28 days. ]
    Plasma Lipopolysaccharide (LPS) after intervention period
  • Gut Permeability [ Time Frame: Change from baseline gut permeability at 24 days of the intervention. ]
    urine lactulose: mannitol ratio.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2014)
  • Plasma Endotoxin Level and Its Panel. [ Time Frame: Change from baseline plasma endotoxin level and it's panel during 28 days. ]
    Plasma LPS, LBP, soluble CD14, IL-6, and TNF-alpha.
  • Gut Permeability [ Time Frame: Change from baseline gut permeability at 24 days of the intervention. ]
    urine for lactulose and mannitol ratio.
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 (Aim2)
Official Title  ICMJE Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Insulin Sensitivity
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Placebo Comparator: Type2 Diabetes Mellitus - Placebo
    Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)
    Intervention: Drug: Maltodextrin
  • Placebo Comparator: Obese with NGT - Placebo
    Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)
    Intervention: Drug: Maltodextrin
  • Placebo Comparator: Lean with NGT -Placebo
    Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)
    Intervention: Drug: Maltodextrin
  • Active Comparator: Type2 Diabetes Mellitus - Synbiotic
    Type 2 Diabetic subjects will receive synbiotic
    Intervention: Drug: Synbiotic
  • Active Comparator: Type2 Diabetes Mellitus - Sevelamer
    Type 2 Diabetic subjects will receive sevelamer
    Intervention: Drug: Sevelamer
  • Active Comparator: Obese with NGT - Synbiotic
    Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic
    Intervention: Drug: Synbiotic
  • Active Comparator: Obese with NGT - Sevelamer
    Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
    Intervention: Drug: Sevelamer
  • Active Comparator: Lean with NGT - Synbiotic
    Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic
    Intervention: Drug: Synbiotic
  • Active Comparator: Lean with NGT - Sevelamer
    Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
    Intervention: Drug: Sevelamer
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 Completed
Actual Enrollment  ICMJE
 (submitted: August 26, 2020)
69
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2014)
108
Actual Study Completion Date  ICMJE September 10, 2018
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 NCT02127125
Other Study ID Numbers  ICMJE HSC20130458H
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party 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 August 2020

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