Pre-Diabetes
Conditions
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.
Interventions
DRUGVancomycin
Vancomycin 3 times a day for 7 days
OTHERPlacebo
Placebo pills identical in appearance to each antibiotics to be taken on the same schedule as each antibiotic
DRUGNeomycin
Neomycin 3 times a day for 1 day
DRUGClindamycin
Clindamycin 3 times a day for 5 days
PROCEDUREFecal Microbiota Transplantation
FMT conducted via colonoscopy
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 10 weeks | Insulin sensitivity measured by standard euglycemic insulin clamp. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microbiome Composition | 7 days | Outcome is reported as the Shannon alpha diversity index (unitless measure) at baseline and 7 days post FMT. |
| Changes in Fecal Bacterial Composition Associated With FMT Overall Antibiotic and Placebo Conditioning Groups) by Laboratory Analysis. | 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. |
| Adverse Event Rates | 10 weeks | Outcome is reported as a patient self report of adverse events over 10 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Antibiotics Prior to FMT One week prior to FMT, a course of three oral antibiotics are taken: Vancomycin 500mg, Neomycin 1000mg, and Clindamycin 300mg.
Vancomycin: Vancomycin 3 times a day for 7 days
Neomycin: Neomycin 3 times a day for 1 day
Clindamycin: Clindamycin 3 times a day for 5 days
Fecal Microbiota Transplantation: FMT conducted via colonoscopy | 7 |
| Placebo Prior to FMT One week prior to FMT, a course of three sugar pills identical to each antibiotic.
Placebo: Placebo pills identical in appearance to each antibiotics to be taken on the same schedule as each antibiotic
Fecal Microbiota Transplantation: FMT conducted via colonoscopy | 5 |
| Total | 12 |
Baseline characteristics
| Characteristic | Antibiotics Prior to FMT | Placebo Prior to FMT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Continuous | 43.7 Years STANDARD_DEVIATION 9.63 | 46.6 Years STANDARD_DEVIATION 7.95 | 44.9 Years STANDARD_DEVIATION 8.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 12 Participants |
| Region of Enrollment United States | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 6 / 7 | 4 / 5 |
| serious Total, serious adverse events | 1 / 7 | 0 / 5 |
Outcome results
Primary
Insulin Sensitivity
Insulin sensitivity measured by standard euglycemic insulin clamp.
Time frame: 10 weeks
Population: Due to errors in formulation of the euglycemic insulin clamp solutions, insulin sensitivity data is not able to be analyzed.
Secondary
Adverse Event Rates
Outcome is reported as a patient self report of adverse events over 10 weeks.
Time frame: 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antibiotics Prior to FMT | Adverse Event Rates | 6 Number of adverse events |
| Placebo Prior to FMT | Adverse Event Rates | 4 Number of adverse events |
Secondary
Changes in Fecal Bacterial Composition Associated With FMT Overall Antibiotic and Placebo Conditioning Groups) by Laboratory Analysis.
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.
Time frame: Baseline and 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antibiotics Prior to FMT | Changes in Fecal Bacterial Composition Associated With FMT Overall Antibiotic and Placebo Conditioning Groups) by Laboratory Analysis. | 5 percent relative abundance | Standard Deviation 2 |
| Placebo Prior to FMT | Changes in Fecal Bacterial Composition Associated With FMT Overall Antibiotic and Placebo Conditioning Groups) by Laboratory Analysis. | 17 percent relative abundance | Standard Deviation 1 |
Secondary
Microbiome Composition
Outcome is reported as the Shannon alpha diversity index (unitless measure) at baseline and 7 days post FMT.
Time frame: 7 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antibiotics Prior to FMT | Microbiome Composition | Baseline | 3.3 unitless measure | Standard Deviation 0.5 |
| Antibiotics Prior to FMT | Microbiome Composition | 7 days post FMT | 3.3 unitless measure | Standard Deviation 0.5 |
| Placebo Prior to FMT | Microbiome Composition | Baseline | 3.3 unitless measure | Standard Deviation 0.5 |
| Placebo Prior to FMT | Microbiome Composition | 7 days post FMT | 1.2 unitless measure | Standard Deviation 0.2 |