Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes
Condition: Type1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      After informed consent is obtained, potential participants will be assessed for eligibility,
      including eliciting medical history, physical examination, and laboratory testing (including
      HbA1c, auto-antibody measurement [unless positive auto-antibody results already available],
      and pregnancy test for females with childbearing potential).

      Participants who already have positive auto-antibodies can be randomized immediately. All
      other participants will be scheduled for a randomization visit after the auto-antibody
      results are available; positive auto-antibodies are required for randomization.

      Eligible participants with body weight ≥30 kg (Cohort A) will be randomly assigned to one of
      4 groups: HCL and placebo, HCL and verapamil, non-HCL and placebo or non-HCL and verapamil.
      Eligible individuals with body weight <30 kg (Cohort B) will be randomly assigned 2:1 to
      either HCL or non-HCL. Randomization schedules will be separate for Cohort A and Cohort B and
      will be stratified by site.

      Participants assigned to HCL will receive intensive diabetes management with frequent
      contacts by study staff with the goal of near-normalization of glucose concentrations.

      Participants assigned to non-HCL will receive a Dexcom G6 continuous glucose monitor (CGM)
      and diabetes management will follow usual care by their personal diabetes health care
      provider.

      Participants will be followed for 12 months from diagnosis, completing a 6 week visit timed
      from randomization and 13, 26, 39, and 52 week visits timed from diagnosis. Participants will
      have a MMTT performed, HbA1c measured, and blood drawn for mechanistic studies at
      Randomization, 13, 26, 39 and 52 weeks. At all follow-up visits, a physical exam will be
      performed, pregnancy testing performed (if indicated), insulin dose (units/kg/day) recorded,
      and device data downloaded.

      Safety assessments will be made throughout the study by querying about episodes of severe
      hypoglycemia and DKA, and overall health.

      Participants already enrolled in the study and using the Medtronic 670G 4.0 AHCL may
      transition to the Medtronic 780G if desired. Contacts will be performed to review CareLink
      data and check for adverse events and device deficiencies on days 1, 3 and 5 after transition
      from 670G 4.0 AHCL to 780G.

      Prior to the 780G system becoming commercially available, study participants using the
      Medtronic system at 52 weeks will have the opportunity to continue using the 780G system at
      home until the system is commercially available OR until the CLVer trial is complete (last
      participant's 52-week visit), whichever comes first.

      Additional Procedures for Cohort A:

      Drug will be double blinded. Drug dose will be weight-dependent and will be escalated at 2-4
      week intervals, up to a weight-dependent maximum if tolerated. Cohort A will have additional
      safety visits 1 week after initiation of study drug and after each study drug dose increase,
      to test blood pressure and pulse.

      Local lab measurement of aspartate aminotransferase/alanine aminotransferase (AST/ALT) and
      creatinine will occur, and an EKG will be performed at Screening, 6, 26, and 52 weeks. Over
      the course of the trial, study drug dose may be decreased or discontinued if side effects
      occur.
    

Intervention name(s): HCL; verapamil 120mg tablet; non-HCL; placebo
Intervention type(s): Device; Drug; Device; Drug
Intervention description(s): Hybrid Closed Loop therapy; verapamil tablet; Usual diabetes care; placebo pill manufactured to mimic verapamil 120mg tablet
Intervention MeSH terms: Verapamil
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: new onset; verapamil; hybrid closed loop; hcl; beta cell; diabetes; children; T1D; c-peptide; pediatric