- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02127125
Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2) (MicroB2)
August 26, 2020 updated by: The University of Texas Health Science Center at San Antonio
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
69
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78229
- Audie L. Murphy VA Hospital, STVHCS
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Type2 Diabetes Mellitus - Placebo
Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)
|
Maltodextrin treatment as a placebo group.
Maltodextrin, 6 gm three times a day for 4 weeks.
|
Placebo Comparator: Obese with NGT - Placebo
Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)
|
Maltodextrin treatment as a placebo group.
Maltodextrin, 6 gm three times a day for 4 weeks.
|
Placebo Comparator: Lean with NGT -Placebo
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)
|
Maltodextrin treatment as a placebo group.
Maltodextrin, 6 gm three times a day for 4 weeks.
|
Active Comparator: Type2 Diabetes Mellitus - Synbiotic
Type 2 Diabetic subjects will receive 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.
|
Active Comparator: Type2 Diabetes Mellitus - Sevelamer
Type 2 Diabetic subjects will receive sevelamer
|
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Names:
|
Active Comparator: Obese with NGT - Synbiotic
Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive 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.
|
Active Comparator: Obese with NGT - Sevelamer
Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
|
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Names:
|
Active Comparator: Lean with NGT - Synbiotic
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive 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.
|
Active Comparator: Lean with NGT - Sevelamer
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
|
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Change from baseline insulin sensitivity at 28 days of the intervention.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Change from baseline plasma endotoxin level and its panel during 28 days.
|
Gut Permeability
Time Frame: Change from baseline gut permeability at 24 days of the intervention.
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urine lactulose: mannitol ratio.
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Change from baseline gut permeability at 24 days of the intervention.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Nicolas Musi, MD., The University of Texas Health Science Center at San Antonio
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 10, 2014
Primary Completion (Actual)
September 1, 2018
Study Completion (Actual)
September 10, 2018
Study Registration Dates
First Submitted
April 24, 2014
First Submitted That Met QC Criteria
April 28, 2014
First Posted (Estimate)
April 30, 2014
Study Record Updates
Last Update Posted (Actual)
September 11, 2020
Last Update Submitted That Met QC Criteria
August 26, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HSC20130458H
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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