Interventional Bioremediation of Microbiota in Metabolic Syndrome
Condition: Pre-Diabetes
MeSH terms: Metabolic Syndrome; Prediabetic State
Intervention: Vancomycin; Placebo; Neomycin; Clindamycin; Fecal Microbiota Transplantation
Intervention description: Vancomycin 3 times a day for 7 days; Placebo pills identical in appearance to each antibiotics to be taken on the same schedule as each antibiotic; Neomycin 3 times a day for 1 day; Clindamycin 3 times a day for 5 days; FMT conducted via colonoscopy
Intervention MeSH terms: Vancomycin; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Neomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether changing the microbial composition in the
      colon can improve metabolism of sugar in people who are on the verge of developing diabetes
      (pre-diabetics). Study participants will undergo a fecal microbiota transplantation (FMT)
      using material from lean donors, as well as a series of tests prior to and after the
      transplant. The investigators will examine any changes in fecal bacterial composition
      associated with FMT and determine if any observed changes have an influence on blood sugar
      metabolism.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide informed consent

          2. Ambulatory and community dwelling

          3. Age 18 - 70 years of age

          4. Able and willing to comply with the study schedule and procedures

          5. Pre-diabetic with fasting blood glucose > 100 mg/dL and/or blood glucose 140-200 mg/dL
             2-hours after ingestion of 75 gm glucose and/or Hemoglobin A1c > 5.7-6.5 percent

        Exclusion Criteria:

          1. Serious, concomitant illness that, in the opinion of the Investigator, would interfere
             with evaluation of safety or efficacy, or put the subject at risk of harm from study
             participation.

          2. Known inflammatory bowel disease (Crohn's disease, ulcerative colitis, lymphocytic
             colitis).

          3. Current abnormal liver tests that may be attributed to a cause other than
             non-alcoholic liver disease. Note: These exclusionary conditions may include viral
             hepatitis, alcoholic liver disease, hemochromatosis, Wilson's disease,
             medication-induced liver test abnormalities, celiac disease.

          4. Renal insufficiency, defined as creatinine ≤ 1.25 mg/dL

          5. Significant alcohol use, defined as > 20 g/day in females and > 30 g/day in males for
             a period of 3 months within one year prior to screening.

          6. Underlying chronic gastrointestinal disease that can cause diarrhea, including short
             bowel syndrome, diarrhea-predominant irritable bowel syndrome, malabsorption, celiac
             disease.

          7. History of partial or complete colectomy.

          8. History of malabsorptive bariatric surgery.

          9. Use of insulin or hypoglycemic medications.

         10. History of anaphylactic food allergies, e.g., peanuts, seafood.

         11. Food intolerances and allergies, including gluten sensitivity, lactose intolerance,
             and intolerance of high fiber dietary content.

         12. Symptomatic problems associated with intestinal gas and bloating.

         13. Irritable bowel syndrome, including diarrhea-dominant, constipation-dominant, and
             mixed.

         14. Functional GI disorder.

         15. Unable to tolerate a colonoscopy.

         16. Presence of an indwelling intravenous line.

         17. Infection requiring antibiotics other than the conditioning antibiotics during the
             study period.

         18. Inability to take vancomycin, neomycin, and clindamycin antibiotics prior to FMT due
             to known hypersensitivity or intolerance.

         19. Major genetic immune dysfunction (e.g., common variable immune deficiency).

         20. Acquired immune deficiencies due to infections such as HIV.

         21. Immunosuppressive medications including one of the following: systemic
             corticosteroids, calcineurin inhibitors, thiopurines, methotrexate, biologics (e.g.,
             anti-tumor necrosis factor drugs), cancer chemotherapy.

         22. Planned use of oral probiotics while on study.

         23. Planned or ongoing chemotherapy for malignancy.

         24. Planned antibiotic therapy within the period of the study, e.g., perioperative
             antibiotics.

         25. Pregnant or lactating. Female participants of child-bearing age and their partners
             will be counseled on contraceptive measures to prevent pregnancy during the study
             period.

         26. History of drug or alcohol abuse in the past 2 years.

         27. Currently participating in another clinical study.

         28. Legally incompetent and unable to understand the study's purpose, significance and
             consequences, and to make decisions accordingly.

         29. Presence of metal implants, such as surgical clips or pacemakers, which will preclude
             performance of MRI tests.

         30. Inability to undergo MRI testing for any reason, e.g., claustrophobia.