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CompletedNCT04233034CLVerUpdated Nov 27, 2024Results posted

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

A Phase 3 interventional study of HCL and verapamil 120mg tablet in Type1 Diabetes, sponsored by Jaeb Center for Health Research. Completed at 6 sites in United States. Open to participants aged 7 Years to 17 Years. Per ClinicalTrials.gov, last updated 2024-11-27.

Sponsored by Jaeb Center for Health Research · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
113
Allocation
Randomized
Ages
7 Years to 17 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Type1 Diabetes

Keywords

  • new onset
  • verapamil
  • hybrid closed loop
  • hcl
  • beta cell
  • diabetes
  • children
  • T1D
  • c-peptide
  • pediatric
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 113 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Jaeb Center for Health Research is the lead sponsor of 126 studies on the registry; 17 are open to participants now.

Of its 16 completed or terminated interventional studies of FDA-regulated products, 14 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
7 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
113 participants (actual)

Study arms

  • Active comparator
    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. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\]

    Device: HCL · Drug: placebo

  • Active comparator
    HCL and verapamil

    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. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\]

    Device: HCL · Drug: verapamil 120mg tablet

  • Active comparator
    non-HCL and verapamil

    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. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\]

    Drug: verapamil 120mg tablet · Device: non-HCL

  • Placebo comparator
    non-HCL and placebo

    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. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\]

    Device: non-HCL · Drug: placebo

Interventions

  • DeviceHCL

    Hybrid Closed Loop therapy

  • Drugverapamil 120mg tablet

    verapamil tablet

  • Devicenon-HCL

    Usual diabetes care

  • Drugplacebo

    placebo pill manufactured to mimic verapamil 120mg tablet

06

What researchers measure

Primary outcomes

  1. C-peptide Area Under the Curve (AUC)

    The primary outcome is the C-peptide in response to a 2-hour MMTT at 52 weeks. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.

    Time frame: 52 weeks

Secondary outcomes

  1. C-peptide AUC

    C-peptide AUC between treatment groups. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.

    Time frame: 13, 26 and 39 weeks

  2. Peak C-peptide

    Maximum of all C-peptide values during the MMTT

    Time frame: 13, 26, 39 weeks and 52 weeks

  3. Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml

    Percentage where maximum of all C-peptide values during the MMTT \>= 0.2 pmol/ml

    Time frame: 13, 26, 39 weeks and 52 weeks

  4. CGM Mean Glucose

    Mean glucose between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  5. Percentage of CGM Time in Range (70-180 mg/dL)

    CGM sensor glucose values from 70 to 180 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  6. Percentage of CGM Time in Range 70-140 mg/dL

    Percentage of CGM sensor glucose values from 70 to 140 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  7. Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks

    Percentage of patients with \>=70% sensor glucose values from 70 to 180 mg/dL between treatment groups

    Time frame: 52 Weeks

  8. Percentage of CGM Time >140 mg/dL

    CGM sensor glucose values \>140 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  9. Percentage of CGM Time >180 mg/dL

    CGM sensor glucose values \>180 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  10. Percentage of CGM Time >250 mg/dL

    Percentage of CGM sensor glucose values \>250 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  11. Percentage of CGM Time <54 mg/dL

    Percentage of CGM sensor glucose values \<54 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  12. Percentage of CGM Time <70 mg/dL

    Percentage of CGM sensor glucose values \<70 mg/dL between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  13. CGM Coefficient of Variation

    Coefficient of variation between treatment groups. Calculated as the standard deviation of CGM glucose values divided by the mean of CGM glucose values.

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  14. HbA1c

    HbA1c between treatment groups

    Time frame: 13, 26, 39 weeks and 52 weeks

  15. Number of Participants With HbA1c <7.0%

    Percentage of participants with HbA1c \< 7.0% between treatment groups

    Time frame: 13, 26, 39 weeks and 52 weeks

  16. Number of Participants With HbA1c <6.5%

    Percentage of participants with HbA1c \< 6.5% between treatment groups

    Time frame: 13, 26, 39 weeks and 52 weeks

  17. Total Daily Insulin Per kg

    Total daily insulin per kg between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  18. Basal:Bolus Ratio

    Ratio of basal:bolus insulin between treatment groups

    Time frame: 6, 13, 26, 39 weeks and 52 weeks

  19. Severe Hypoglycemia

    Frequency of episodes of severe hypoglycemia between treatment groups

    Time frame: 52 weeks

  20. DKA

    Frequency of episodes of DKA between treatment groups

    Time frame: 52 weeks

07

Results

Posted Nov 27, 2024

Participant flow

Participant flow — Overall Study
MilestoneHCL and PlaceboHCL and VerapamilNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL Only
Started20222521196
Completed20212319196
Not completed012200

Outcome measures

PrimaryC-peptide Area Under the Curve (AUC)

The primary outcome is the C-peptide in response to a 2-hour MMTT at 52 weeks. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.

Time frame:
52 weeks
Reported as:
Geometric mean · (pmol/ml)*minutes
C-peptide Area Under the Curve (AUC)
(pmol/ml)*minutesHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization0.57 ± 0.220.60 ± 0.180.66 ± 0.200.60 ± 0.22
52 Weeks0.45 ± 0.300.50 ± 0.310.65 ± 0.310.44 ± 0.30
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = 0.89 · Mean difference (final values): -0.01 · 95% CI -0.11 to 0.10Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.04 · Mean difference (final values): 0.14 · 95% CI 0.01 to 0.27Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryC-peptide AUC

C-peptide AUC between treatment groups. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.

Time frame:
13, 26 and 39 weeks
Reported as:
Geometric mean · (pmol/ml)*minutes
C-peptide AUC
(pmol/ml)*minutesHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization0.57 ± 0.220.60 ± 0.180.66 ± 0.200.60 ± 0.22
Week 130.63 ± 0.230.69 ± 0.250.75 ± 0.260.69 ± 0.23
Week 260.62 ± 0.280.63 ± 0.280.77 ± 0.300.62 ± 0.25
Week 390.51 ± 0.300.57 ± 0.300.71 ± 0.310.52 ± 0.28
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = 0.80 (P-value adjusted for multiplicity using the Benjamini-Hochberg procedure.) · Mean difference (final values): -0.01 · 95% CI -0.10 to 0.08Mean difference (HCL - Non-HCL) at 13 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = 0.80 (P-value adjusted for multiplicity using the Benjamini-Hochberg procedure.) · Mean difference (final values): 0.03 · 95% CI -0.08 to 0.13Mean difference (HCL - Non-HCL) at 26 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = 0.80 (P-value was adjusted for multiplicity using the Benjamini-Hochberg procedure.) · Mean difference (final values): -0.02 · 95% CI -0.13 to 0.09Mean difference (HCL - Non-HCL) at 39 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.69 (P-value adjusted for multiplicity using the Benjamini-Hochberg procedure.) · Mean difference (final values): 0.02 · 95% CI -0.09 to 0.13Mean difference (Verapamil - Placebo) at 13 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.08 (P-value was adjusted for multiplicity using the Benjamini-Hochberg procedure.) · Mean difference (final values): 0.12 · 95% CI -0.02 to 0.25Mean difference (Verapamil - Placebo) at 26 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.08 (P-value adjusted for multiplicity using the Benjamini-Hochberg procedure.) · Mean difference (final values): 0.14 · 95% CI -0.01 to 0.28Mean difference (Verapamil - Placebo) at 39 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryPeak C-peptide

Maximum of all C-peptide values during the MMTT

Time frame:
13, 26, 39 weeks and 52 weeks
Reported as:
Mean · pmol/mL
Peak C-peptide
pmol/mLHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization0.72 ± 0.250.78 ± 0.230.96 ± 0.300.89 ± 0.27
13 Weeks0.81 ± 0.270.87 ± 0.290.84 ± 0.240.78 ± 0.27
26 Weeks0.78 ± 0.340.76 ± 0.330.97 ± 0.350.76 ± 0.30
39 Weeks0.65 ± 0.350.69 ± 0.350.89 ± 0.360.63 ± 0.32
52 Weeks0.56 ± 0.360.62 ± 0.370.83 ± 0.370.55 ± 0.34
SecondaryNumber of Participants With a Peak C-peptide >= 0.2 Pmol/ml

Percentage where maximum of all C-peptide values during the MMTT \>= 0.2 pmol/ml

Time frame:
13, 26, 39 weeks and 52 weeks
Reported as:
Count of participants · Participants
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
ParticipantsHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization60514640
13 Weeks58504539
26 Weeks56474437
39 Weeks49384131
52 Weeks45364127
SecondaryCGM Mean Glucose

Mean glucose between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · mg/dL
CGM Mean Glucose
mg/dLHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks129 ± 12139 ± 29131 ± 23132 ± 22
13 Weeks132 ± 15140 ± 26134 ± 22134 ± 22
26 Weeks135 ± 17152 ± 35138 ± 32144 ± 27
39 Weeks140 ± 19161 ± 36141 ± 23155 ± 38
52 Weeks145 ± 19167 ± 42151 ± 27159 ± 41
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = <0.001 · Mean difference (final values): -25 · 95% CI -37 to -14Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.74 · Mean difference (final values): -4 · 95% CI -25 to 16Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryPercentage of CGM Time in Range (70-180 mg/dL)

CGM sensor glucose values from 70 to 180 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percent of Time
Percentage of CGM Time in Range (70-180 mg/dL)
Percent of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks86 ± 884 ± 985 ± 1584 ± 13
13 Weeks84 ± 979 ± 1683 ± 1584 ± 13
26 Weeks83 ± 1073 ± 2081 ± 1778 ± 17
39 Weeks80 ± 1168 ± 2180 ± 1572 ± 20
52 Weeks78 ± 1164 ± 2274 ± 1870 ± 21
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = <0.001 · Mean difference (final values): 16 · 95% CI 10 to 22Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.74 · Mean difference (final values): 2 · 95% CI -9 to 13Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryPercentage of CGM Time in Range 70-140 mg/dL

Percentage of CGM sensor glucose values from 70 to 140 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percentage of Time
Percentage of CGM Time in Range 70-140 mg/dL
Percentage of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks69 ± 1160 ± 2267 ± 1966 ± 18
13 Weeks67 ± 1359 ± 2265 ± 1965 ± 19
26 Weeks64 ± 1351 ± 2161 ± 2057 ± 19
39 Weeks60 ± 1446 ± 2158 ± 1951 ± 20
52 Weeks56 ± 1343 ± 2151 ± 1949 ± 21
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = <0.001 · Mean difference (final values): 16 · 95% CI 10 to 22Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.95 · Mean difference (final values): 0 · 95% CI -8 to 14Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryNumber of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks

Percentage of patients with \>=70% sensor glucose values from 70 to 180 mg/dL between treatment groups

Time frame:
52 Weeks
Reported as:
Count of participants · Participants
Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks
ParticipantsHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks46223023
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Regression, Logistic · p = <0.001 · Risk difference (rd): 0.38 · 95% CI 0.21 to 0.53
  • Verapamil vs Placebo · Regression, Logistic · p = 0.79 · Risk difference (rd): 0.03 · 95% CI -0.26 to 0.32
SecondaryPercentage of CGM Time >140 mg/dL

CGM sensor glucose values \>140 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percent of Time
Percentage of CGM Time >140 mg/dL
Percent of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks29 ± 1138 ± 2332 ± 1932 ± 18
13 Weeks32 ± 1340 ± 2234 ± 1933 ± 20
26 Weeks34 ± 1347 ± 2236 ± 2041 ± 20
39 Weeks38 ± 1453 ± 2140 ± 1947 ± 21
52 Weeks42 ± 1456 ± 2247 ± 1949 ± 22
SecondaryPercentage of CGM Time >180 mg/dL

CGM sensor glucose values \>180 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percent of Time
Percentage of CGM Time >180 mg/dL
Percent of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks12 ± 819 ± 1913 ± 1514 ± 14
13 Weeks14 ± 919 ± 1715 ± 1515 ± 14
26 Weeks15 ± 1025 ± 2017 ± 1721 ± 18
39 Weeks18 ± 1130 ± 2119 ± 1526 ± 21
52 Weeks20 ± 1134 ± 2225 ± 1828 ± 21
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = <0.001 · Mean difference (final values): -16 · 95% CI -22 to -9Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.74 · Mean difference (final values): -2 · 95% CI -13 to 9Mean difference at 52 weeks (verapamil - placebo) adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryPercentage of CGM Time >250 mg/dL

Percentage of CGM sensor glucose values \>250 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percent of Time
Percentage of CGM Time >250 mg/dL
Percent of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks1 ± 23 ± 41 ± 12 ± 3
13 Weeks2 ± 33 ± 42 ± 22 ± 3
26 Weeks2 ± 36 ± 82 ± 34 ± 6
39 Weeks3 ± 39 ± 123 ± 47 ± 9
52 Weeks4 ± 410 ± 135 ± 68 ± 10
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = 0.003 · Mean difference (final values): -4 · 95% CI -7 to -1Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.74 · Mean difference (final values): -1 · 95% CI -6 to 4Mean difference (verapamil - placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryPercentage of CGM Time <54 mg/dL

Percentage of CGM sensor glucose values \<54 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percent of Time
Percentage of CGM Time <54 mg/dL
Percent of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks0.22 ± 0.220.11 ± 0.130.14 ± 0.160.16 ± 0.16
13 Weeks0.23 ± 0.210.12 ± 0.160.19 ± 0.200.16 ± 0.19
26 Weeks0.25 ± 0.250.10 ± 0.110.22 ± 0.250.14 ± 0.18
39 Weeks0.32 ± 0.340.16 ± 0.200.21 ± 0.270.26 ± 0.27
52 Weeks0.29 ± 0.340.18 ± 0.210.20 ± 0.240.24 ± 0.26
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Regression, Linear · p = 0.23 · Mean difference (final values): 0.06 · 95% CI -0.04 to 0.17Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Regression, Linear · p = 0.79 · Mean difference (final values): -0.2 · 95% CI -1.0 to 0.6Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryPercentage of CGM Time <70 mg/dL

Percentage of CGM sensor glucose values \<70 mg/dL between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percent of Time
Percentage of CGM Time <70 mg/dL
Percent of TimeHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks1.7 ± 1.01.5 ± 1.61.5 ± 1.51.7 ± 1.6
13 Weeks1.6 ± 1.21.2 ± 1.11.4 ± 0.91.4 ± 1.5
26 Weeks1.9 ± 1.11.2 ± 1.01.6 ± 1.41.4 ± 1.2
39 Weeks2.0 ± 1.31.2 ± 1.31.5 ± 1.41.7 ± 1.6
52 Weeks1.8 ± 1.21.4 ± 1.41.3 ± 1.21.6 ± 1.3
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Regression, Linear · p = 0.39 · Mean difference (final values): 0.2 · 95% CI -0.3 to 0.7Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Regression, Linear · p = 0.74 · Mean difference (final values): -0.2 · 95% CI -1.0 to 0.6Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryCGM Coefficient of Variation

Coefficient of variation between treatment groups. Calculated as the standard deviation of CGM glucose values divided by the mean of CGM glucose values.

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Coefficient of Variation Percentage
CGM Coefficient of Variation
Coefficient of Variation PercentageHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
6 Weeks31 ± 530 ± 628 ± 530 ± 6
13 Weeks31 ± 630 ± 729 ± 629 ± 6
26 Weeks32 ± 532 ± 630 ± 631 ± 5
39 Weeks34 ± 633 ± 631 ± 633 ± 5
52 Weeks34 ± 633 ± 532 ± 633 ± 5
SecondaryHbA1c

HbA1c between treatment groups

Time frame:
13, 26, 39 weeks and 52 weeks
Reported as:
Mean · Percentage of Glycosylated Hemoglobin
HbA1c
Percentage of Glycosylated HemoglobinHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization10.3 ± 1.310.2 ± 1.610.3 ± 1.710.2 ± 1.2
13 Weeks6.4 ± 0.56.5 ± 0.96.3 ± 0.86.4 ± 0.6
26 Weeks6.4 ± 0.66.6 ± 1.06.3 ± 0.96.5 ± 0.8
39 Weeks6.6 ± 0.77.0 ± 1.26.4 ± 0.97.0 ± 1.1
52 Weeks6.5 ± 0.77.1 ± 1.36.6 ± 1.06.9 ± 1.2
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = <0.001 · Mean difference (final values): -0.7 · 95% CI -1.1 to -0.3Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.65 · Mean difference (final values): -0.3 · 95% CI -1.0 to 0.4Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryNumber of Participants With HbA1c <7.0%

Percentage of participants with HbA1c \< 7.0% between treatment groups

Time frame:
13, 26, 39 weeks and 52 weeks
Reported as:
Count of participants · Participants
Number of Participants With HbA1c <7.0%
ParticipantsHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization2130
13 Weeks48363832
26 Weeks45313725
39 Weeks44233322
52 Weeks42263223
SecondaryNumber of Participants With HbA1c <6.5%

Percentage of participants with HbA1c \< 6.5% between treatment groups

Time frame:
13, 26, 39 weeks and 52 weeks
Reported as:
Count of participants · Participants
Number of Participants With HbA1c <6.5%
ParticipantsHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization0000
13 Weeks27242720
26 Weeks37233122
39 Weeks33203018
52 Weeks28192518
SecondaryTotal Daily Insulin Per kg

Total daily insulin per kg between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Mean · U/kg/day
Total Daily Insulin Per kg
U/kg/dayHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization0.68 ± 0.280.66 ± 0.300.74 ± 0.290.64 ± 0.27
6 Weeks0.54 ± 0.260.55 ± 0.330.55 ± 0.330.54 ± 0.28
13 Weeks0.51 ± 0.230.53 ± 0.250.54 ± 0.250.54 ± 0.26
26 Weeks0.61 ± 0.280.53 ± 0.230.57 ± 0.280.58 ± 0.29
39 Weeks0.68 ± 0.320.58 ± 0.270.59 ± 0.290.66 ± 0.32
52 Weeks0.74 ± 0.320.64 ± 0.250.65 ± 0.260.74 ± 0.34
Statistical analysis
  • HCL and Intensive Management vs Non-HCL and Standard Care · Mixed Models Analysis · p = 0.07 · Mean difference (final values): 0.09 · 95% CI -0.01 to 0.20Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.
  • Verapamil vs Placebo · Mixed Models Analysis · p = 0.52 · Mean difference (final values): -0.12 · 95% CI -0.30 to 0.05Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.
SecondaryBasal:Bolus Ratio

Ratio of basal:bolus insulin between treatment groups

Time frame:
6, 13, 26, 39 weeks and 52 weeks
Reported as:
Number · Daily Basal/Bolus Ratio
Basal:Bolus Ratio
Daily Basal/Bolus RatioHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Randomization0.961.01.11.1
6 Weeks0.611.10.890.85
13 Weeks0.6110.890.82
26 Weeks0.590.850.720.75
39 Weeks0.670.720.750.72
52 Weeks0.690.750.820.72
SecondarySevere Hypoglycemia

Frequency of episodes of severe hypoglycemia between treatment groups

Time frame:
52 weeks
Reported as:
Number · Number of Severe Hypoglycemic Events
Severe Hypoglycemia
Number of Severe Hypoglycemic EventsHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
Severe Hypoglycemia1111
SecondaryDKA

Frequency of episodes of DKA between treatment groups

Time frame:
52 weeks
Reported as:
Number · Number of DKA Events
DKA
Number of DKA EventsHCL and Intensive ManagementNon-HCL and Standard CareVerapamilPlacebo
DKA1101

Adverse events

Collected over Adverse event data where collected during the 52 week RCT phase.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
HCL and Verapamil0/22 (0%)3/22 (13.6%)20/22 (90.9%)
HCL and Placebo0/20 (0%)1/20 (5%)16/20 (80%)
Non-HCL and Verapamil0/25 (0%)1/25 (4%)19/25 (76%)
Non-HCL and Placebo0/21 (0%)3/21 (14.3%)14/21 (66.7%)
HCL Only0/19 (0%)1/19 (5.3%)18/19 (94.7%)
Non-HCL Only0/6 (0%)0/6 (0%)4/6 (66.7%)
Most frequent serious events
Most frequent serious events
EventHCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL Only
Suicidal IdeationPsychiatric disorders2/220/201/251/210/190/6
Diabetic KetoacidosisEndocrine disorders0/220/200/251/211/190/6
AsthmaRespiratory, thoracic and mediastinal disorders0/221/200/250/210/190/6
HypoglycemiaEndocrine disorders1/220/200/251/210/190/6
KetosisMetabolism and nutrition disorders0/220/200/251/210/190/6
DepressionPsychiatric disorders1/220/201/250/210/190/6
Most frequent other events
Showing 10 of 107
Most frequent other events
EventHCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL Only
ColdRespiratory, thoracic and mediastinal disorders1/221/203/253/213/192/6
FeverGeneral disorders1/221/202/252/215/191/6
CoughRespiratory, thoracic and mediastinal disorders1/220/200/251/215/190/6
Upper Respiratory InfectionRespiratory, thoracic and mediastinal disorders3/225/201/251/211/191/6
Covid-19Infections and infestations3/224/206/253/213/190/6
HeadacheNervous system disorders3/223/201/254/213/190/6
LipohypertrophySkin and subcutaneous tissue disorders0/220/201/254/211/190/6
Otitis ExternaEar and labyrinth disorders0/220/200/250/210/191/6
Celiac DiseaseGastrointestinal disorders0/221/200/250/213/191/6
KetosisMetabolism and nutrition disorders0/221/202/251/211/191/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Mean13 ± 312 ± 213 ± 313 ± 28 ± 19 ± 112 ± 3
Sex: Female, Male
Sex: Female, Male(Participants)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Female8912710349
Male141113149364
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Race/Ethnicity — White1614201515686
Race/Ethnicity — Black/African American1110104
Race/Ethnicity — Hispanic42441015
Race/Ethnicity — Asian0100001
Race/Ethnicity — American Indian/Alaskan Native1000001
Race/Ethnicity — More than One0202206
Annual Household Income
Annual Household Income(Participants)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
<$50,00053522017
$50,000-<$100,00053465326
>=$100,000121215812362
Missing0215008
Highest Parental Education
Highest Parental Education(Participants)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Less than Bachelor's67662128
Bachelor's10611108348
Advanced Degree67859237
Health Insurance
Health Insurance(Participants)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Private1619221814392
Public41335218
None2000002
Missing0000011
BMI Percentile at Randomization
BMI Percentile at Randomization(Percentile)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Median78 (34 to 90)53 (21 to 86)58 (33 to 89)65 (37 to 80)43 (22 to 47)32 (26 to 37)56 (28 to 85)
Time Since Diagnosis at Randomization (days)
Time Since Diagnosis at Randomization (days)(Days)HCL and VerapamilHCL and PlaceboNon-HCL and VerapamilNon-HCL and PlaceboHCL OnlyNon-HCL OnlyTotal
Mean24 ± 524 ± 524 ± 525 ± 423 ± 523 ± 524 ± 5

5 further baseline measures are reported on the registry.

08

Study locations

6 sites
  • Stanford University
    Palo Alto, California 94304, United States
  • Barbara Davis Center
    Aurora, Colorado 80045, United States
  • Yale University
    New Haven, Connecticut 06511, United States
  • Indiana University
    Indianapolis, Indiana 46202, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Children's Mercy Hospital
    Kansas City, Missouri 64111, United States
09

References and documents

Study documents

  • Study protocol · Mar 1, 2022
  • Statistical analysis plan · Sep 27, 2022

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 27, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04233034
Lead sponsor
Jaeb Center for Health Research
Collaborators
Juvenile Diabetes Research Foundation, University of Minnesota, DexCom, Inc., Medtronic, Tandem Diabetes Care, Inc.
Responsible party
Sponsor
First posted
Jan 18, 2020
Start date
Jul 9, 2020
Primary completion
Sep 15, 2022
Completion
Sep 30, 2022
Results posted
Nov 27, 2024
Last update
Nov 27, 2024

Study contacts

Antoinette Moran, MD
study chair · University of Minnesota
Gregory Forlenza, MD
study chair · Barbara Davis Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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