Evaluation of a Novel Insulin Sensitizer in People With Type 1 Diabetes (WBH003)

Evaluation of a Novel Insulin Sensitizer on Glycemic Control, Insulin Usage, and Cardiovascular Biomarkers in People With Type 1 Diabetes Who Use Closed-loop Automated Insulin Delivery

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.

Study Overview

• Status: Recruiting
• Conditions: Insulin; Cardiovascular Health; Type 1 Diabetes (T1D); Glycemic Control for Diabetes Mellitus; Ketones
• Intervention / Treatment: Drug: Placebo; Drug: CIR-0602K

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

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lee Hartline, MEd; Phone Number: 14349245247; Email: LMH9D@VIRGINIA.EDU

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Contact: Horton B Horton, MD; Phone Number: (434) 924-1828; Email: WBH2N@VIRGINIA.EDU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CIR-0602K; CIR-0602K 250 mg daily	Drug: CIR-0602K; mitochondrial pyruvate carrier inhibitor
Placebo Comparator: Placebo; Matching Placebo Tablet	Drug: Placebo; Placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Time-in-Range	Glucose time 70-180 mg/dL	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Daily Insulin Dose	Units of insulin per day	12 weeks
Glucose Time-above-Range	Glucose time >180 mg/dL	12 weeks
Glucose Time-Below-Range	Glucose time <70 mg/dL	12 weeks
Hemoglobin A1c	measure of glycemic control	12 weeks
Insulin Sensitivity	M-value from euglycemic insulin clamp	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial Artery Flow-Mediated Dilation	Noninvasive measurement of blood vessel function	12 weeks
Carotid-Femoral Pulse Wave Velocity	Noninvasive measure of aortic stiffness	12 weeks
Radial Artery Augmentation Index	Noninvasive measure of radial artery stiffness	12 weeks
C-peptide	Blood test that measures endogenous insulin secretion	12 weeks
Daily fasting ketone level	Measure of blood ketone level collected by fingerstick meter conducted at home each morning	12 weeks
Cardiovascular Biomarkers	IL-6, TNF-alpha, hsCRP, E-selectin, ICAM-1, adiponectin	12 weeks
Peripheral Blood Mononuclear Cells	CD14++CD16-	12 weeks

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: William B. Horton, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: September 12, 2025
• First Submitted That Met QC Criteria: September 18, 2025
• First Posted (Actual): September 22, 2025

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Type 1 Diabetes; cardiovascular health; adjunct therapy; closed loop technology; time-in-range
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Acid-Base Imbalance; Acidosis; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Insulin Resistance; Ketosis
• Other Study ID Numbers: 302645; 3-SRA-2025-1773-M-B (Other Grant/Funding Number: Breakthrough T1D)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The investigative team will finalize the decision (as to whether or not to share IPD) at a later date. Of note, IPD in this study qualifies as protected health information and would thus require safety considerations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No