Type1 DiabetesPhase 3CLVerNCT04233034

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

A Phase 3 study testing HCL, verapamil 120mg tablet and non-HCL in people with Type1 Diabetes, run by Jaeb Center for Health Research at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 7 to 17 years
Conditions the study is for: Type1 Diabetes
What is being tested?: HCL, verapamil 120mg tablet and non-HCL
Type of treatment: Pill or oral medicine, Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 113 participants
Where: 6 sitesUnited States
Study dates: 9 Jul 2020to 30 Sep 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 7 to 17 years
All sexes
No healthy volunteers
Child

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
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

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

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

Other trials in United States

About this study

Official title: Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes (CLVer)

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.

Conditions: Type1 Diabetes
Being tested: HCL, verapamil 120mg tablet, non-HCL, placebo
Keywords: new onset, verapamil, hybrid closed loop, hcl, beta cell, diabetes, children, T1D, c-peptide, pediatric
Medical subject headings: Leukemia, Hairy Cell, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HCLDevice
Hybrid Closed Loop therapy
verapamil 120mg tabletDrug
verapamil tablet
non-HCLDevice
Usual diabetes care
placeboDrug
placebo pill manufactured to mimic verapamil 120mg tablet

Study groups in NCT04233034
Study group	Role	What they receive
HCL and placebo	Active comparator	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.] Receives: Device: HCL; Drug: placebo
HCL and verapamil	Active comparator	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.] Receives: Device: HCL; Drug: verapamil 120mg tablet
non-HCL and verapamil	Active comparator	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.] Receives: Drug: verapamil 120mg tablet; Device: non-HCL
non-HCL and placebo	Placebo comparator	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.] Receives: Device: non-HCL; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 52 weeks

Secondary outcomes (20)

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.
Measured: 13, 26 and 39 weeks
Peak C-peptide
Maximum of all C-peptide values during the MMTT
Measured: 13, 26, 39 weeks and 52 weeks
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
Measured: 13, 26, 39 weeks and 52 weeks
CGM Mean Glucose
Mean glucose between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time in Range (70-180 mg/dL)
CGM sensor glucose values from 70 to 180 mg/dL between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
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
Measured: 6, 13, 26, 39 weeks and 52 weeks
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
Measured: 52 Weeks
Percentage of CGM Time >140 mg/dL
CGM sensor glucose values >140 mg/dL between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time >180 mg/dL
CGM sensor glucose values >180 mg/dL between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time >250 mg/dL
Percentage of CGM sensor glucose values >250 mg/dL between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time <54 mg/dL
Percentage of CGM sensor glucose values <54 mg/dL between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time <70 mg/dL
Percentage of CGM sensor glucose values <70 mg/dL between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
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.
Measured: 6, 13, 26, 39 weeks and 52 weeks
HbA1c
HbA1c between treatment groups
Measured: 13, 26, 39 weeks and 52 weeks
Number of Participants With HbA1c <7.0%
Percentage of participants with HbA1c < 7.0% between treatment groups
Measured: 13, 26, 39 weeks and 52 weeks
Number of Participants With HbA1c <6.5%
Percentage of participants with HbA1c < 6.5% between treatment groups
Measured: 13, 26, 39 weeks and 52 weeks
Total Daily Insulin Per kg
Total daily insulin per kg between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Basal:Bolus Ratio
Ratio of basal:bolus insulin between treatment groups
Measured: 6, 13, 26, 39 weeks and 52 weeks
Severe Hypoglycemia
Frequency of episodes of severe hypoglycemia between treatment groups
Measured: 52 weeks
DKA
Frequency of episodes of DKA between treatment groups
Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Jul 202030 Sep 2022

First posted18 Jan 2020
Study start9 Jul 2020
Primary completion15 Sep 2022
Study completion30 Sep 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Type1 DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 113 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04233034
Sponsor's protocol ID: CLVer
Acronym: CLVer
Status last verified: Nov 2024
First submitted: 14 Jan 2020
Last updated: 27 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: Yes

Publications

Ekhlaspour L, Buckingham B, Bauza C, Clements M, Forlenza GP, Neyman A, Norlander L, Schamberger M, Sherr JL, Bailey R, Beck RW, Kollman C, Beasley S, Cobry E, DiMeglio LA, Paprocki E, Van Name M, Moran A; CLVer Study Group. Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience. J Clin Transl Endocrinol. 2024 May 18;36:100352. doi: 10.1016/j.jcte.2024.100352. eCollection 2024 Jun.
PubMed 38860154
Forlenza GP, McVean J, Beck RW, Bauza C, Bailey R, Buckingham B, DiMeglio LA, Sherr JL, Clements M, Neyman A, Evans-Molina C, Sims EK, Messer LH, Ekhlaspour L, McDonough R, Van Name M, Rojas D, Beasley S, DuBose S, Kollman C, Moran A; CLVer Study Group. Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023 Mar 28;329(12):990-999. doi: 10.1001/jama.2023.2064.
PubMed 36826844
McVean J, Forlenza GP, Beck RW, Bauza C, Bailey R, Buckingham B, DiMeglio LA, Sherr JL, Clements M, Neyman A, Evans-Molina C, Sims EK, Messer LH, Ekhlaspour L, McDonough R, Van Name M, Rojas D, Beasley S, DuBose S, Kollman C, Moran A; CLVer Study Group. Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023 Mar 28;329(12):980-989. doi: 10.1001/jama.2023.2063.
PubMed 36826834

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes (CLVer)
ClinicalTrials.gov ID: NCT04233034
Acronym / sponsor ID: CLVer / CLVer
Conditions: Type1 Diabetes
Keywords: new onset, verapamil, hybrid closed loop, hcl, beta cell, diabetes, children, T1D
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 113 participants (actual)
Lead sponsor: Jaeb Center for Health ResearchUniversity, hospital or other
Collaborators: Juvenile Diabetes Research Foundation, University of Minnesota, DexCom, Inc., Medtronic, Tandem Diabetes Care, Inc.
Study start: 9 Jul 2020 (actual)
Primary completion: 15 Sep 2022 (actual)
Study completion: 30 Sep 2022 (actual)
First posted: 18 Jan 2020 (actual)
Results: Posted 27 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Safety assessments will be made throughout the study by querying about episodes of severe hypoglycemia and DKA, and overall health.

Additional Procedures for Cohort A:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
HCL and placebo	Active comparator	Device: HCL, Drug: placeboParticipants 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.]
HCL and verapamil	Active comparator	Device: HCL, Drug: verapamil 120mg tabletParticipants 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.]
non-HCL and verapamil	Active comparator	Drug: verapamil 120mg tablet, Device: non-HCLParticipants 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.]
non-HCL and placebo	Placebo comparator	Device: non-HCL, Drug: placeboParticipants 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.]

Who may qualify

Ages: 7 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
HCLHybrid Closed Loop therapy	Device	HCL and placebo, HCL and verapamil
verapamil 120mg tabletverapamil tablet	Drug	HCL and verapamil, non-HCL and verapamil
non-HCLUsual diabetes care	Device	non-HCL and placebo, non-HCL and verapamil
placeboplacebo pill manufactured to mimic verapamil 120mg tablet	Drug	HCL and placebo, non-HCL and placebo

Primary outcome

C-peptide Area Under the Curve (AUC)
Time frame: 52 weeks
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.

20 secondary outcomes

C-peptide AUC
Time frame: 13, 26 and 39 weeks
Peak C-peptide
Time frame: 13, 26, 39 weeks and 52 weeks
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
Time frame: 13, 26, 39 weeks and 52 weeks
CGM Mean Glucose
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time in Range (70-180 mg/dL)
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time in Range 70-140 mg/dL
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks
Time frame: 52 Weeks
Percentage of CGM Time >140 mg/dL
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time >180 mg/dL
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time >250 mg/dL
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time <54 mg/dL
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Percentage of CGM Time <70 mg/dL
Time frame: 6, 13, 26, 39 weeks and 52 weeks
CGM Coefficient of Variation
Time frame: 6, 13, 26, 39 weeks and 52 weeks
HbA1c
Time frame: 13, 26, 39 weeks and 52 weeks
Number of Participants With HbA1c <7.0%
Time frame: 13, 26, 39 weeks and 52 weeks
Number of Participants With HbA1c <6.5%
Time frame: 13, 26, 39 weeks and 52 weeks
Total Daily Insulin Per kg
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Basal:Bolus Ratio
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Severe Hypoglycemia
Time frame: 52 weeks
DKA
Time frame: 52 weeks

Results and safety

Results posted to the registry on 27 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HCL and Placebo	20	20
HCL and Verapamil	22	21
Non-HCL and Verapamil	25	23
Non-HCL and Placebo	21	19
HCL Only	19	19
Non-HCL Only	6	6

Primary outcome: C-peptide Area Under the Curve (AUC)

Time frame: 52 weeks. Geometric mean (Standard Deviation). Unit: (pmol/ml)*minutes

Measure	HCL and Intensive Management n = 61	Non-HCL and Standard Care n = 51	Verapamil n = 47	Placebo n = 40
Randomization	0.57 (0.22)	0.60 (0.18)	0.66 (0.20)	0.60 (0.22)
52 Weeks	0.45 (0.30)	0.50 (0.31)	0.65 (0.31)	0.44 (0.30)

HCL and Intensive Management vs Non-HCL and Standard Care: Mean Difference (Final Values): -0.01 (95% CI -0.11 to 0.10), p = 0.89, Mixed Models Analysis
Verapamil vs Placebo: Mean Difference (Final Values): 0.14 (95% CI 0.01 to 0.27), p = 0.04, Mixed Models Analysis

Population analysed: 1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was not analyzed. All other participants with at least one available measurement of C-Peptide AUC were included in the analysis model.

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data where collected during the 52 week RCT phase.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HCL and Verapamil	3 of 22 (13.6%)	20 of 22 (90.9%)	0 of 22
HCL and Placebo	1 of 20 (5%)	16 of 20 (80%)	0 of 20
Non-HCL and Verapamil	1 of 25 (4%)	19 of 25 (76%)	0 of 25
Non-HCL and Placebo	3 of 21 (14.3%)	14 of 21 (66.7%)	0 of 21
HCL Only	1 of 19 (5.3%)	18 of 19 (94.7%)	0 of 19
Non-HCL Only	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38860154Ekhlaspour L, Buckingham B, Bauza C, Clements M, Forlenza GP, Neyman A, Norlander L, Schamberger M, Sherr JL, Bailey R, Beck RW, Kollman C, Beasley S, Cobry E, DiMeglio LA, Paprocki E, Van Name M, Moran A; CLVer Study Group. Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience. J Clin Transl Endocrinol. 2024 May 18;36:100352. doi: 10.1016/j.jcte.2024.100352. eCollection 2024 Jun.
Derived from this study: PubMed 36826844Forlenza GP, McVean J, Beck RW, Bauza C, Bailey R, Buckingham B, DiMeglio LA, Sherr JL, Clements M, Neyman A, Evans-Molina C, Sims EK, Messer LH, Ekhlaspour L, McDonough R, Van Name M, Rojas D, Beasley S, DuBose S, Kollman C, Moran A; CLVer Study Group. Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023 Mar 28;329(12):990-999. doi: 10.1001/jama.2023.2064.
Derived from this study: PubMed 36826834McVean J, Forlenza GP, Beck RW, Bauza C, Bailey R, Buckingham B, DiMeglio LA, Sherr JL, Clements M, Neyman A, Evans-Molina C, Sims EK, Messer LH, Ekhlaspour L, McDonough R, Van Name M, Rojas D, Beasley S, DuBose S, Kollman C, Moran A; CLVer Study Group. Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023 Mar 28;329(12):980-989. doi: 10.1001/jama.2023.2063.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Antoinette Moran, MD study chair

University of Minnesota

Gregory Forlenza, MD study chair

Barbara Davis Center

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing HCL, verapamil 120mg tablet and non-HCL in people with Type1 Diabetes, run by Jaeb Center for Health Research at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

C-peptide Area Under the Curve (AUC) (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04233034, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2024.