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Trial record 2 of 4 for:    sevelamer AND insulin

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

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.

Condition or disease Intervention/treatment Phase
Insulin Sensitivity Drug: Maltodextrin Drug: Synbiotic Drug: Sevelamer Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
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)
Actual Study Start Date : April 10, 2014
Actual Primary Completion Date : September 2018
Actual Study Completion Date : September 10, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sevelamer

Arm Intervention/treatment
Placebo Comparator: Type2 Diabetes Mellitus - Placebo
Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)
Drug: Maltodextrin
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)
Drug: Maltodextrin
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)
Drug: Maltodextrin
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
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.

Active Comparator: Type2 Diabetes Mellitus - Sevelamer
Type 2 Diabetic subjects will receive sevelamer
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 - Synbiotic
Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic
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.

Active Comparator: Obese with NGT - Sevelamer
Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
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 - Synbiotic
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic
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.

Active Comparator: Lean with NGT - Sevelamer
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
Drug: Sevelamer
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Name: Renvela




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older 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.

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


Locations
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United States, Texas
Audie L. Murphy VA Hospital, STVHCS
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
American Diabetes Association
Investigators
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Principal Investigator: Nicolas Musi, MD. The University of Texas Health Science Center at San Antonio
  Study Documents (Full-Text)

Documents provided by The University of Texas Health Science Center at San Antonio:
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Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02127125    
Other Study ID Numbers: HSC20130458H
First Posted: April 30, 2014    Key Record Dates
Results First Posted: September 11, 2020
Last Update Posted: September 11, 2020
Last Verified: August 2020
Additional relevant MeSH terms:
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Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Sevelamer
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action