Back to resultsMechanism of Microbiome-induced Insulin Resistance in Humans (Aim2) (MicroB2)
Primary Purpose
Insulin Sensitivity
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Maltodextrin
Synbiotic
Sevelamer
Sponsored by
About this trial
This is an interventional treatment trial for Insulin Sensitivity
Eligibility 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.
Sites / Locations
- Audie L. Murphy VA Hospital, STVHCS
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Placebo Comparator
Placebo Comparator
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Type2 Diabetes Mellitus - Placebo
Obese with NGT - Placebo
Lean with NGT -Placebo
Type2 Diabetes Mellitus - Synbiotic
Type2 Diabetes Mellitus - Sevelamer
Obese with NGT - Synbiotic
Obese with NGT - Sevelamer
Lean with NGT - Synbiotic
Lean with NGT - Sevelamer
Arm Description
Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)
Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)
Type 2 Diabetic subjects will receive synbiotic
Type 2 Diabetic subjects will receive sevelamer
Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic
Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
Outcomes
Primary Outcome Measures
Insulin Sensitivity
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.
Secondary Outcome Measures
Plasma Endotoxin Level and Its Panel.
Plasma Lipopolysaccharide (LPS) after intervention period
Gut Permeability
urine lactulose: mannitol ratio.
Full Information
NCT ID
NCT02127125
First Posted
April 24, 2014
Last Updated
August 26, 2020
Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
American Diabetes Association
1. Study Identification
Unique Protocol Identification Number
NCT02127125
Brief Title
Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Acronym
MicroB2
Official Title
Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
April 10, 2014 (Actual)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
September 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
American Diabetes Association
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Sensitivity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Type2 Diabetes Mellitus - Placebo
Arm Type
Placebo Comparator
Arm Description
Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)
Arm Title
Obese with NGT - Placebo
Arm Type
Placebo Comparator
Arm Description
Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)
Arm Title
Lean with NGT -Placebo
Arm Type
Placebo Comparator
Arm Description
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)
Arm Title
Type2 Diabetes Mellitus - Synbiotic
Arm Type
Active Comparator
Arm Description
Type 2 Diabetic subjects will receive synbiotic
Arm Title
Type2 Diabetes Mellitus - Sevelamer
Arm Type
Active Comparator
Arm Description
Type 2 Diabetic subjects will receive sevelamer
Arm Title
Obese with NGT - Synbiotic
Arm Type
Active Comparator
Arm Description
Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic
Arm Title
Obese with NGT - Sevelamer
Arm Type
Active Comparator
Arm Description
Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
Arm Title
Lean with NGT - Synbiotic
Arm Type
Active Comparator
Arm Description
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic
Arm Title
Lean with NGT - Sevelamer
Arm Type
Active Comparator
Arm Description
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
Intervention Type
Drug
Intervention Name(s)
Maltodextrin
Intervention Description
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Synbiotic
Intervention Description
Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Sevelamer
Other Intervention Name(s)
Renvela
Intervention Description
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Primary Outcome Measure Information:
Title
Insulin Sensitivity
Description
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.
Time Frame
Change from baseline insulin sensitivity at 28 days of the intervention.
Secondary Outcome Measure Information:
Title
Plasma Endotoxin Level and Its Panel.
Description
Plasma Lipopolysaccharide (LPS) after intervention period
Time Frame
Change from baseline plasma endotoxin level and its panel during 28 days.
Title
Gut Permeability
Description
urine lactulose: mannitol ratio.
Time Frame
Change from baseline gut permeability at 24 days of the intervention.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas Musi, MD.
Organizational Affiliation
The University of Texas Health Science Center at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
Audie L. Murphy VA Hospital, STVHCS
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
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