Clinical trial NCT02127125: Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Official title: Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Insulin Sensitivity
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2014-04-30
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: Change from baseline insulin sensitivity at 28 days of the intervention.
Secondary outcomes:
measure: Plasma Endotoxin Level and Its Panel.
timeFrame: Change from baseline plasma endotoxin level and its panel during 28 days.
measure: Gut Permeability
timeFrame: Change from baseline gut permeability at 24 days of the intervention.
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Audie L. Murphy VA Hospital, STVHCS
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Nicolas Musi, MD.
role: PRINCIPAL_INVESTIGATOR
References: