Butyrate Adjuvant Therapy for Type 1 Diabetes

This study will test effect of BKR-017 (colon-targeted 500 mg butyrate tablets) as adjuvant therapy in type 1 diabetes (TID) Subjects on metabolic control in this population. Insulin sensitivity, glucose control (variability) and triglycerides will be measured after 7 weeks of treatment and compared to baseline.

• BKR-017 (Drug), also known as Butyrate tablets: BKR-017

Primary outcomes

• Insulin Sensitivity [Day 0 to Day 48]: Change in Insulin sensitivity as measured by estimated glucose disposal rate (eGDR), a validated clinical tool for estimating insulin sensitivity in Type 1 Diabetes.

Secondary outcomes

• Glucose Variability [Day 0 to Day 48]: Change in glucose measured by Hemoglobin A1c (HbA1c) which is a blood test that measures blood glucose levels.
• Change in Triglycerides [Day 0 to Day 28]: The change in triglycerides levels was measured through blood samples taken at Day 0 and Day 28.

Sex: All, ages: 20 Years to 80 Years

Inclusion Criteria:

1. Diagnosed with T1D and under the care of a healthcare professional for its management
2. HbA1c 6.4-8.9%, inclusive
3. Has given written informed consent to participate in this study
4. Willing to complete 28-day baseline period and 48 -day test period
5. Willing to maintain current diet and exercise routine for the duration of the study
6. Current use of a Dexcom Continuous Glucose Monitor (CGM)

Exclusion Criteria:

1. History of bariatric or intestinal surgery
2. Active gastrointestinal disease including but not limited to irritable bowel syndrome, inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), diverticulitis, gastroparesis, or chronic/frequent diarrhea or chronic/frequent constipation
3. Active and clinically significant hepatic, pancreatic disease, or renal disease as determined by the investigator
4. History of significant heart disease, including congestive heart failure, prior MI, chronic atrial or ventricular fibrillation, coronary artery disease, cerebral vascular disease, or other cardiovascular disease, that in the opinion of the investigator should exclude the subject from the study
5. Severely uncontrolled hypertension at screening defined as a systolic blood pressure > 180 mmHg or a diastolic blood pressure > 110 mmHg on the average of two seated measurements after being at rest for at least 5 minutes
6. Uncontrolled hyperthyroidism or hypothyroidism, or other significant thyroid disease
7. Active significant infection as determined by the investigator
8. Known allergy to butyrate or any of the components of the tablets
9. Participation in a clinical trial and/or treatment with an investigational drug during the 30 days before screening, or within 5 half-lives of receipt of an investigational drug or twice the duration of the biological effect of any investigational drug (whichever is longer)
10. Pregnant, nursing, or trying to become pregnant
11. Presence of pitting edema on physical exam
12. High fiber diet
13. In the investigator's judgment, the subject is not suitable for the study for any other reason or cannot commit to the requirements of the study.
14. Subject is taking one or more of the excluded therapies.

Participant flow

Outcome results

• Insulin Sensitivity (Primary), Mean, mg/kg/min: Conventional Therapy / Butyrate 5.71 +/- 2.05
• Glucose Variability (Secondary), Mean, percentage of hemoglobin: Conventional Therapy / Butyrate 7.1 +/- 0.2
• Change in Triglycerides (Secondary), Mean, mg/dL: Conventional Therapy / Butyrate 83.5 +/- 9.0

Adverse events

Time frame: Adverse events were collected from the time of administration of a subject's first dose of test product until study completion, approximately 48 days.

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2023-07-13)

• Adrian Vella, MD, Principal investigator, Mayo Clinic