Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes

• Status: Active, not recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Randomized trial of youth aged 7-<18 years with newly diagnosed stage 3 type 1 diabetes (T1D) to assess the effect of both (1) near-normalization of glucose concentrations achieved through use of a hybrid closed loop (HCL) system and (2) verapamil on preservation of β-cell function 12 months after diagnosis. Participants with body weight ≥30 kg (Cohort A) will be randomly assigned in a factorial design to (1) HCL plus intensive diabetes management or usual care with no HCL and (2) verapamil or placebo. Participants with body weight <30 kg (Cohort B) will be randomly assigned 2:1 in a parallel group design to HCL plus intensive diabetes management or to usual care with no HCL.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jaeb Center for Health Research
• Collaborators: DexCom, Inc.; Juvenile Diabetes Research Foundation; Medtronic; Tandem Diabetes Care, Inc.; University of Minnesota
• Treatments: Verapamil

Criteria

• Participant Inclusion Criteria:

1. New-onset stage 3 T1D within 21 days of diagnosis (timed from start of insulin therapy), with ability to be randomized within 31 days of diagnosis (time from diagnosis to screening can be longer provided all screening testing can be completed within 31 days of diagnosis)

2. At least one positive type 1 diabetes auto-antibody

3. Age 7 - <18 years at the time of enrollment

4. Willing to have a parent or legal guardian provide informed consent and child assent

5. In a female participant with childbearing potential, not currently pregnant and willing to avoid pregnancy and breastfeeding and undergo pregnancy testing throughout the study

6. English speaking/reading

7. Able to swallow pills (tested with an inert imitation tablet in clinic prior to randomization)

8. Willing to not use any non-insulin glucose-lowering agents

9. Willing to use an insulin approved for the pump (if assigned to HCL)

10. Willing to avoid medications containing acetaminophen, and no contraindications for ibuprofen use (in case assigned to Medtronic HCL system)

• Participant Exclusion Criteria:

1. Ongoing use of medications known to influence glucose tolerance such as systemic steroids

2. Other systemic disease which in the opinion of the investigator precludes participation (including psychiatric illness)

3. Unwilling to abstain from use of HCL therapy for 12 months

a. Personal pump and CGM use, including systems with a "suspend-before-low" function, will be allowed for participants randomized to non-HCL groups

4. "Silent" diabetes-i.e., Stage 3 diabetes that is identified by routine oral glucose tolerance testing (OGTT) or in the course of surveillance studies but is not accompanied by fasting hyperglycemia or classic symptoms of diabetes

5. Participation in another research study that involves diabetes care

• Additional exclusion criteria for Cohort A:

1. Blood pressure (either systolic or diastolic) <5th percentile for age, gender, and height on two out of three measurements

2. Pulse <2nd percentile for age and gender on two out of three measurements

3. History of vasovagal syncopal episodes related to hypotension

4. Abnormal EKG rhythm unless cleared for study participation by a cardiologist

5. Underlying cardiac disease (ex. left ventricular dysfunction, hypertrophic cardiomyopathy), certain arrhythmias (ex. Atrioventricular block (AV) block, accessory pathway such as Wolff-Parkinson-White or Lown-Ganong-Levine syndromes), known liver dysfunction, known renal impairment, Duchenne's muscular dystrophy, active Graves disease or hyperthyroidism, and untreated hypothyroidism

6. Estimated glomerular filtration rate (eGFR) < 90

7. AST and/or ALT greater than 1.5 times the upper limit of normal

8. Need to use of any of the following medications during the study: beta blocker, seizure medication (carbamazepine, phenobarbital, phenytoin), other antihypertensive medications, HMG-CoA reductase inhibitors, lithium, theophylline, clonidine, or aspirin

9. Any known hypersensitivity reaction to Verapamil