Interventional Bioremediation of Microbiota in Metabolic Syndrome

• ClinicalTrials.gov Identifier: NCT02730962
• Recruitment Status: Terminated
• First Posted: April 7, 2016
• Results First Posted: November 20, 2020
• Last Update Posted: February 22, 2023
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pre-Diabetes	Drug: Vancomycin; Other: Placebo; Drug: Neomycin; Drug: Clindamycin; Procedure: Fecal Microbiota Transplantation	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Interventional Bioremediation of Microbiota in Metabolic Syndrome
• Study Start Date: June 2016
• Actual Primary Completion Date: January 2018
• Actual Study Completion Date: January 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Antibiotics prior to FMT; One week prior to FMT, a course of three oral antibiotics are taken: Vancomycin 500mg, Neomycin 1000mg, and Clindamycin 300mg.	Drug: Vancomycin; Vancomycin 3 times a day for 7 days; Drug: Neomycin; Neomycin 3 times a day for 1 day; Drug: Clindamycin; Clindamycin 3 times a day for 5 days; Procedure: Fecal Microbiota Transplantation; FMT conducted via colonoscopy
Placebo Comparator: Placebo prior to FMT; One week prior to FMT, a course of three sugar pills identical to each antibiotic.	Other: Placebo; Placebo pills identical in appearance to each antibiotics to be taken on the same schedule as each antibiotic; Procedure: Fecal Microbiota Transplantation; FMT conducted via colonoscopy

Outcome Measures

Primary Outcome Measures :

1. Insulin Sensitivity [ Time Frame: 10 weeks ]
   Insulin sensitivity measured by standard euglycemic insulin clamp.

Secondary Outcome Measures :

1. Microbiome Composition [ Time Frame: 7 days ]
   Outcome is reported as the Shannon alpha diversity index (unitless measure) at baseline and 7 days post FMT.
2. Changes in Fecal Bacterial Composition Associated With FMT Overall Antibiotic and Placebo Conditioning Groups) by Laboratory Analysis. [ Time Frame: Baseline and 10 weeks ]
   Microbiome composition was assessed post FMT using fecal DNA extraction and sequences. Outcome is reported as the change in relative abundance of the family Ruminococcaceae.
3. Adverse Event Rates [ Time Frame: 10 weeks ]
   Outcome is reported as a patient self report of adverse events over 10 weeks.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Minnesota

University of Minnesota Medical Center

Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Alexander Khoruts, MD; University of Minnesota

  Study Documents (Full-Text)

Documents provided by University of Minnesota:

Study Protocol and Statistical Analysis Plan  [PDF] May 19, 2016

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT02730962
• Other Study ID Numbers: GI-2015-22791
• First Posted: April 7, 2016
• Results First Posted: November 20, 2020
• Last Update Posted: February 22, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Metabolic Syndrome; Prediabetic State; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Vancomycin; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Neomycin; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action