Clinical trial NCT02730962: Interventional Bioremediation of Microbiota in Metabolic Syndrome
Official title: Interventional Bioremediation of Microbiota in Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pre-Diabetes
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2016-04-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: 10 weeks
Secondary outcomes:
measure: Microbiome Composition
timeFrame: 7 days
measure: Changes in Fecal Bacterial Composition Associated With FMT Overall Antibiotic and Placebo Conditioning Groups) by Laboratory Analysis.
timeFrame: Baseline and 10 weeks
measure: Adverse Event Rates
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Alexander Khoruts, MD
role: PRINCIPAL_INVESTIGATOR
References: