Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes (CLVer)
Type1 Diabetes
About this trial
This is an interventional treatment trial for Type1 Diabetes focused on measuring new onset, verapamil, hybrid closed loop, hcl, beta cell, diabetes, children, T1D, c-peptide, pediatric
Eligibility Criteria
Participant Inclusion Criteria:
- 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)
- At least one positive type 1 diabetes auto-antibody
- Age 7 - <18 years at the time of enrollment
- Willing to have a parent or legal guardian provide informed consent and child assent
- In a female participant with childbearing potential, not currently pregnant and willing to avoid pregnancy and breastfeeding and undergo pregnancy testing throughout the study
- English speaking/reading
- Able to swallow pills (tested with an inert imitation tablet in clinic prior to randomization)
- Willing to not use any non-insulin glucose-lowering agents
- Willing to use an insulin approved for the pump (if assigned to HCL)
- Willing to avoid medications containing acetaminophen, and no contraindications for ibuprofen use (in case assigned to Medtronic HCL system)
Participant Exclusion Criteria:
- Ongoing use of medications known to influence glucose tolerance such as systemic steroids
- Other systemic disease which in the opinion of the investigator precludes participation (including psychiatric illness)
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
- "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
- Participation in another research study that involves diabetes care
Additional exclusion criteria for Cohort A:
- Blood pressure (either systolic or diastolic) <5th percentile for age, gender, and height on two out of three measurements
- Pulse <2nd percentile for age and gender on two out of three measurements
- History of vasovagal syncopal episodes related to hypotension
- Abnormal EKG rhythm unless cleared for study participation by a cardiologist
- 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
- Estimated glomerular filtration rate (eGFR) < 90
- AST and/or ALT greater than 1.5 times the upper limit of normal
- 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
- Any known hypersensitivity reaction to Verapamil
Sites / Locations
- Stanford University
- Barbara Davis Center
- Yale University
- Indiana University
- University of Minnesota
- Children's Mercy Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
HCL and placebo
HCL and verapamil
non-HCL and verapamil
non-HCL and placebo
Participants assigned to HCL group will initially be randomly assigned 1:1 to use either the Tandem t:slim X2 with Control-IQ technology or a Medtronic HCL system (Medtronic 670G 4.0 AHCL (prior to protocol version 5.0) or Medtronic 780G (starting with protocol version 5.0)). This group will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations. Placebo will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets. Whether drug is active or placebo is blinded to both participant and site. [Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.]
Participants assigned to HCL group will initially be randomly assigned 1:1 to use either the Tandem t:slim X2 with Control-IQ technology or a Medtronic HCL system (Medtronic 670G 4.0 AHCL (prior to protocol version 5.0) or Medtronic 780G (starting with protocol version 5.0)). This group will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations. Verapamil will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets. Whether drug is active or placebo is blinded to both participant and site. [Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.]
Participants assigned to non-HCL will receive a Dexcom G6 CGM and diabetes management will follow usual care by their personal diabetes health care provider. Verapamil will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets. Whether drug is active or placebo is blinded to both participant and site. [Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.]
Participants assigned to non-HCL will receive a Dexcom G6 CGM and diabetes management will follow usual care by their personal diabetes health care provider. Placebo will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets. Whether drug is active or placebo is blinded to both participant and site. [Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.]