A randomised, double-blind, placebo controlled, parallel group, multi-centre trial in adult subjects with newly diagnosed type 1 diabetes mellitus investigating the effect of Verapamil SR on preservation of beta-cell function (VER-A-T1D)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Graz

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Metabolism [G03]

Trial duration

28 Jan 2025 → 17 Apr 2026

Decision date (initial)

2025-01-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

"Innovative Medicines Initiative 2" (Call: IMI2-Call1: Grant Agreement Number: 115797)

External identifiers

EU CT number

2023-506545-27-01

EudraCT number

2020-000435-45

ClinicalTrials.gov

NCT04545151

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To determine the changes in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) at baseline and after 12 months for 360mg Verapamil SR administered orally once daily versus placebo.

Secondary objectives 4

1. To determine the effects of 360mg Verapamil SR administered orally once daily on fasting C-peptide and Dried Blood Spot (DBS) C-peptide measurements over time.
2. To determine the effects of 360mg Verapamil SR administered orally once daily on HbA1c daily total insulin dose and continous glucose monitoring (CGM) time in range.
3. To determine the effects of treatment on other biomarkers related to immunological changes and beta-cell death and survival in this population.
4. To determine the effects of 360mg Verapamil SR administered orally once daily on safety (vital signs, ECG).

Conditions and MedDRA coding

Diabetes mellitus, Type 1

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Have given written informed consent
2. 2. Age ≥18 and <45 years at consent
3. 3. Must have a diagnosis of T1D of within 6 weeks duration at screening (from date of the first insulin injection)
4. 4. Must have at least one or more of the following diabetes-related autoantibodies present at screening: GADA, IA-2A and/or ZnT8A
5. 5. Must have fasting C-peptide levels ≥100 pmol/L measured at screening
6. 6. Be willing to comply with intensive diabetes management

Exclusion criteria 20

1. 1. Be immunodeficient or have clinically significant chronic lymphopenia: Leukopenia (< 3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL), or thrombocytopenia (<100,000 platelets/μL)
2. 2. Have active signs or symptoms of acute infection at the time of screening
3. 3. Be currently pregnant or lactating, or anticipate getting pregnant during the 12 months study period
4. 4. Require use of immunosuppressive agents including chronic use of systemic steroids
5. 5. Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection
6. 6. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, chronic obstructive pulmonary disease (COPD), sickle cell disease, neurological, or blood count abnormalities, as judged by the investigator
7. 7. Have persistent history of malignancies other than skin
8. 8. History of liver insufficiency or laboratory evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal
9. 9. History of renal insufficiency or evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal
10. 10. Current or ongoing use of non-insulin pharmaceuticals that affect glycaemic control within prior 7 days of screening
11. 11. Use of any other investigational drug in the previous 30 days and/or intent on using any investigational drug for the duration of the trial
12. 12. Current use of Verapamil or other calcium channel blockers
13. 13. Known hypersensitivity to Verapamil or to any of its excipients
14. 14. Concomitant medication known for significantly inducing or inhibiting CYP3A4 and/or glycoprotein-P metabolism
15. 15. Intake of grapefruit juice, licorice, St.John’s Wort, cannabidiol, ginkgo biloba
16. 16. Substrate intake of CYP3A4 and/or glycoprotein-P metabolism, as judged by the investigator
17. 17. Hypotension (of less than 100mmHg systolic), sick sinus syndrome (except patients with a functioning artificial pacemaker), uncompensated heart failure or severe left ventricular dysfunction; marked bradycardia (less than 50 beats/minute), atrial flutter or atrial fibrillation in the presence of an accessory bypass tract (e.g. Wolff-Parkinson-White syndrome), hypertrophic cardiomyopathy, acute myocardial infarction, attenuated neuromuscular transmission (e.g. by myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy)
18. 18. ECG second or third degree atrioventricular block; Incomplete branch block.
19. 19. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results.
20. 20. Current use of ß-blockers.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT) after 12 months therapy compared to placebo

Secondary endpoints 13

1. The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT) at 3, 6, 9 months
2. Proinsulin , Insulin, Pro-IAPP and Proglucagon secretion during the first two hours of a mixed meal tolerance test (MMTT) at baseline and 3, 6, 9 an 12 months
3. Fasting C-peptide after 12 months therapy compared to placebo
4. The DBS C-peptide measurements at all observation times
5. Change in HbA1c baseline to 12 months
6. Number of treatment emergent severe hypoglycaemic episodes. Severe hypoglycaemia denotes severe cognitive impairment requiring external assistance for recovery according to the American Diabetes Association (ADA)
7. Number of treatment emergent episodes of diabetic ketoacidosis (DKA)
8. Change in insulin requirements, baseline to 12 months as the daily total dose (three days average) in units per kg BW
9. Change in T1D associated autoantibodies (GADA, IAA, IA-2A and ZnT8A) from baseline to 12 months
10. CGM time in range (70-180 mg/dL, 3.9-10.0 mmol/L) and (70-140 mg/dL, 3.9-7.8 mmol/L), time above range (>180 mg/dL, >10.0 mmol/L), time below range (<70 mg/dL, < 3.9 mmol/L)
11. The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT) at 24 months
12. Change in HbA1c baseline to 24 months
13. Change in insulin requirements, baseline to 24 months as the daily total dose (three days average) in units per kg BW

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Graz

Sponsor organisation

Medical University Of Graz

Address

Neue Stiftingtalstrasse 6

City

Graz

Postcode

8010

Country

Austria

Scientific contact point

Organisation

Medical University Of Graz

Contact name

Chief Investigator

Public contact point

Organisation

Medical University Of Graz

Contact name

Trial Management

Locations

5 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 75 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications