Cardiovascular Health, Glycemic Control for Diabetes Mellitus, Insulin, Ketones, Type 1 Diabetes (T1D)
Conditions
Keywords
Type 1 Diabetes, closed loop technology, time-in-range, adjunct therapy, cardiovascular health
Brief summary
The purpose of this study is to see if the study drug CIR-0602K will improve glucose time-in-range and/or lower total daily insulin dose in people with type 1 diabetes who are using closed-loop automated insulin delivery. Researchers will compare CIR-0602K to a placebo (a look-alike substance that contains no drug) to see if it achieves the investigational endpoints. If the study results show that the drug works to increase time-in-range and lower insulin doses, this will lead to further studies which may then make the drug available to the public.
Detailed description
Participants in the study will: * Come to the Clinical Research Unit (CRU) at UVA Medical Center for 3 visits: Screening, Baseline (Admission 1) and End-of-Study (Admission 2). * Complete various tests of cardiovascular health at each visit. * Take either an experimental drug (CIR-0602K) or placebo for 12 weeks. * Wear a study CGM with their personal insulin pump for 12 weeks. * Be given a ketone meter and strips and be asked to take a fingerstick ketone reading every morning for 12 weeks. * The study team will contact the participants regularly during the study to check their health and how they are tolerating the study drug/placebo. * Return the study CGM, ketone meter, and remaining supplies, etc. at the end of the study. * Notify the study team of any illness, injury, hypoglycemic or hyperglycemic events during the study
Interventions
DRUGCIR-0602K
mitochondrial pyruvate carrier inhibitor
DRUGPlacebo
Placebo tablet
Sponsors
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Clinical research team
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. History of type 1 diabetes for at least one year 4. Age 18-45 years 5. HbA1c \<10% * BMI 18-35 kg/m2. Within this criterion, participants must have either BMI ≥25 or total daily insulin dose of ≥0.5 units/kg/day. * Currently utilizing closed-loop AID therapy that is compatible with Dexcom G7 CGM. * On stable regimen of non-diabetic medications for the last 6 months. * All screening labs within normal limits or not clinically significant. * Ability to take oral medication and be willing to adhere to the study drug/placebo for 12 weeks. * For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 2 weeks after the end of CIR-0602K administration. * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study intervention. * Agreement to adhere to Lifestyle Considerations throughout study duration.
Exclusion criteria
* Current Pregnancy or currently breastfeeding. * History of smoking tobacco products within the last two years. * History of alcohol abuse or illicit drug abuse within 6 months of screening. * Known history of human immunodeficiency virus (HIV). * History of other significant disease (e.g., cardiac, cerebrovascular, gastrointestinal, liver, renal, or endocrine) that could, in the investigator's view, alter study outcomes * Any surgical or medical condition which may significantly alter the absorption of the study drug including but not limited to the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active inflammatory bowel syndrome. * Current use of any antihyperglycemic medication beyond insulin (i.e., GLP-1 receptor agonists, SGLT2 inhibitors, etc.). * Unstable doses (i.e., dose change within the last 4 months) of vasoactive medications (e.g., calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, diuretics, nitrates, alpha-blockers, beta-blockers, etc.). * Daily use of anti-inflammatory medications (e.g., ibuprofen, aspirin, prednisone, dexamethasone, etc.). * Diagnosis of peripheral neuropathy (assessed by screening monofilament exam). * Macroalbuminuria (i.e., urine albumin: creatinine \>300 mg per g). * Retinopathy beyond mild, nonproliferative retinopathy. * History of Level 3 hypoglycemia within the last 12 months. * History of diabetic ketoacidosis (DKA) within the last 12 months. * Screening electrocardiogram (ECG) findings indicative of arrhythmia, sinus node disease, or ischemic heart disease. * Screening oxygen saturation \<90% * History of hypersensitivity or prior adverse reaction to the study drug, closely-related compounds, or any of the stated ingredients. * Use of concomitant medications with a known significant metabolism by CYP2C8 or CYP2C (including paclitaxel, phenytoin, warfarin, celecoxib, tolbutamide, or repaglinide) for the duration of the study. * Participation in an investigational study (other than a non-treatment registry study) or received an investigational drug withing 30 days or 5 half-lives (whichever is longer) prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Time-in-Range | 12 weeks | Glucose time 70-180 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Insulin Dose | 12 weeks | Units of insulin per day |
| Glucose Time-above-Range | 12 weeks | Glucose time \>180 mg/dL |
| Glucose Time-Below-Range | 12 weeks | Glucose time \<70 mg/dL |
| Hemoglobin A1c | 12 weeks | measure of glycemic control |
| Insulin Sensitivity | 12 weeks | M-value from euglycemic insulin clamp |
Countries
United States
Contacts
CONTACTLee Hartline, MEd
PRINCIPAL_INVESTIGATORWilliam B. Horton, MD
University of Virginia
Outcome results
None listed