Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Condition: Insulin Sensitivity
MeSH terms: Insulin Resistance
Intervention: Maltodextrin; Synbiotic; Sevelamer
Intervention description: Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.; Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.; Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Intervention MeSH terms: Sevelamer
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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.