Verapamil SR in Adults With Type 1 Diabetes

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)

Sponsors

Lead Sponsor: Medical University of Graz

Collaborator: Juvenile Diabetes Research Foundation

Source Medical University of Graz
Brief Summary

This study has been set up within the framework of the INNODIA network. INNODIA is a global partnership between 27 academic institutions, 4 industrial partners, a small sized enterprise and 2 patient organisations, bringing their knowledge and experience together with one common goal: "To fight type 1 diabetes". (www.innodia.eu) The overall aim of INNODIA is to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D).

For this, INNODIA has established a comprehensive and interdisciplinary network of clinical and basic scientists, who are leading experts in the field of T1D research in Europe and UK (United Kingdom), with complementary expertise from the areas of immunology, Beta-cell biology, biomarker research and T1D therapy, joining forces in a coordinated fashion with industry partners and two foundations, as well as with all major stakeholders in the process, including regulatory bodies and patients with T1D and their families.

Detailed Description

The study is a multicenter, randomized, double-blind, placebo-controlled study in volunteers with newly diagnosed diabetes mellitus type 1 (within 6 weeks after diagnosis).

The purpose of the clinical trial is to confirm the effect of 360mg Verapamil sustained release (SR) administered orally once daily (titrated over the first 3 months from 120 mg to 360 mg) on the preservation of beta-cell function measured as stimulated C-peptide after 12 months compared to placebo.

The study has a cross-over design and a duration of approximately 24 months, consisting of 3 telephone visits and 7 visits at the trial site. The duration of the treatment phase with verapamil is 12 months, and an additional (optional) follow-up visit will be carried out 12 months after completion of the study. The study procedures are identical in all 20 clinical centres across Europe and the UK.

Overall Status Not yet recruiting
Start Date November 2020
Completion Date May 2023
Primary Completion Date November 2022
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Area under the stimulated C-peptide response curve At 12 months
Secondary Outcome
Measure Time Frame
Area under the stimulated C-peptide response curve At 3, 6, 9 and 24 months
Proinsulin and preproinsulin secretion At baseline and 3, 6, 9 and 12 months
Fasting C-peptide At 12 months
DBS C-peptide At baseline, week 4, week 8, and 3, 6, and 9 months
Change in HbA1c Baseline, 12 and 24 months
Severe hypoglycaemic episodes Baseline to 12 months
DKA Baseline to 12 months
Change in insulin requirements Baseline, 12 and 24 months
Change in T1D associated autoantibodies Baseline to 12 months
Continous glucose monitoring (CGM) At Baseline and every 2 weeks prior to each visit (week 4, week 8, and 3, 6, and 9 months)
Enrollment 138
Condition
Intervention

Intervention Type: Drug

Intervention Name: Verapamil SR

Description: Study drug will be provided in blisters and packaged and labelled. Each package will be labeled as required per country requirement. Labels will be blinded. Drug adminstration: from Day 0 to Week 4: 120 mg once daily from Week 4 to Week 8: 240 mg once daily from Week 8 to Month 12: 360 mg once daily

Arm Group Label: Verapamil SR

Other Name: Isoptin retard 120 mg

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo will be provided in blisters and packaged and labelled. Each package will be labeled as required per country requirement. Labels will be blinded. Drug adminstration: from Day 0 to Week 4: 120 mg once daily from Week 4 to Week 8: 240 mg once daily from Week 8 to Month 12: 360 mg once daily

Arm Group Label: Placebo

Other Name: Matching Placebo for Verapamil SR

Eligibility

Criteria:

Inclusion Criteria:

- Have given written informed consent

- Age ≥18 and <45 years at consent

- Must have a diagnosis of T1D of within 6 weeks duration at screening (from date of the first insulin injection)

- Must have at least one or more diabetes-related autoantibodies present at screening

- Must have random C-peptide levels ≥200 pmol/L measured at screening

- Be willing to comply with intensive diabetes management

Exclusion Criteria:

- 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)

- Have active signs or symptoms of acute infection at the time of screening

- Be currently pregnant or lactating, or anticipate getting pregnant during the 12 months study period

- Require use of immunosuppressive agents including chronic use of systemic steroids

- Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection

- 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

- Have a history of malignancies other than skin

- Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal

- Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal

- Current or ongoing use of non-insulin pharmaceuticals that affect glycaemic control within prior 7 days of screening

- 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

- Current use of verapamil or other calcium channel blockers

- Known hypersensitivity to verapamil or to any of the excipients, use of beta-blockers in patients with poor ventricular function, concomitant ingestion of grapefruit juice, combination with ivabradine

- Hypotension (of less than 90mmHg systolic), sick sinus syndrome (except in patients with a functioning artificial pacemaker); uncompensated heart failure; marked bradycardia (less than 50 beats/minute), Wolff-Parkinson-White syndrome, acute myocardial infarction complicated by bradycardia, marked hypotension or left ventricular failure

- ECG second or third degree atrioventricular block

- Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

Gender: All

Minimum Age: 18 Years

Maximum Age: 45 Years

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Martina Brunner, MSc

Phone: +43 316 385

Phone Ext.: 72841

Email: [email protected]

Location
Facility: Contact: Investigator:
Medical University of Graz, Department of Internal Medicine Division of Endocrinology and Metabolism | Graz, Styria, 8010, Austria Silvia Leitgeb, MSc +43316385 80363 [email protected] Thomas Pieber, MD, Prof Principal Investigator Gerlies Treiber, MD, Prof Sub-Investigator Eva Novak, MD Sub-Investigator Harald Sourij, MD, Prof Sub-Investigator Felix Aberer, MD, Prof Sub-Investigator Daniel Hochfellner, MD Sub-Investigator
Universite Libre de Bruxelles | Bruxelles, Belgium Aicha Hamouda [email protected] Miriam Cnop, MD, Prof. Principal Investigator
Katholieke Universiteit | Leuven, Belgium Hilde Morobe [email protected] Chantal Mathieu, MD, Prof. Principal Investigator
Institut National de la Sante er de la Recherche Medicale | Paris, France Anna Jones [email protected] Roberto Mallone, MD Principal Investigator
HKA Hannover | Hanover, Germany Bärbel Aschemeier [email protected] Thomas Danne, MD, Prof. Principal Investigator
Universität Ulm | Ulm, Germany Stefanie Lanzinger [email protected] Reinhard Holl, MD, Prof. Principal Investigator
Università vita salute San Raffaele | Milano, Italy Sabina Martinenghi [email protected] Emanuele Bosi, MD, Prof. Principal Investigator
Università degli Studi di Siena | Siena, Italy Caterina Formichi [email protected] Francesco Dotta, MD, Prof. Principal Investigator
Slaski Uniwersytet Medyczny w Katowicach | Katowice, Poland Grażyna Deja [email protected] Przemyslawa Jarosz-Chobot, MD, Prof. Principal Investigator
Lunds Universität | Lund, Sweden Markus Lundgren [email protected] Markus Lundgren, MD Principal Investigator
Queen Elizabeth Hospital | Birmingham, United Kingdom Kathy Draxlbauer [email protected] Parth Narendran, Dr. Principal Investigator
Southmead Hospital | Bristol, United Kingdom Schenede Coppin [email protected] Danijela Tatovic, Dr. Principal Investigator
Addenbrokes Hospital | Cambridge, United Kingdom Jane Kennet [email protected] Mark Evans, Dr. Principal Investigator
University Hospital of Wales | Cardiff, United Kingdom Colin Dayan [email protected] Colin Dayan, MD, Prof. Principal Investigator
Bart's Hospital QMUL | London, United Kingdom Melanie Pattrick [email protected] David Leslie, MD, Prof. Principal Investigator
Guy's Hospital | London, United Kingdom Olanike Okolo [email protected] Yuk-Fun Liu, Dr. Principal Investigator
Queens Medical Centre | Nottingham, United Kingdom Tasso Gazis [email protected] Tasso Gazis, Dr. Principal Investigator
OCDEM, John Radcliffe Hospital | Oxford, United Kingdom Katharine Owen [email protected] Katharine Owen, MD, Prof. Principal Investigator
Royal Hallamshire Hospital | Sheffield, United Kingdom Sharon Caunt [email protected] Simon Heller, MD, Prof. Principal Investigator
Singleton Hospital | Swansea, United Kingdom Scott Davies [email protected] Steve Bain, MD, Prof. Principal Investigator
Location Countries

Austria

Belgium

France

Germany

Italy

Poland

Sweden

United Kingdom

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Verapamil SR

Type: Experimental

Description: Eligible participants will be randomised into the verapamil SR arm and receive instructions on frequency of administration (daily intake). 80 participants on the experimental arm are expected to complete the trial.

Label: Placebo

Type: Placebo Comparator

Description: Eligible participants will be randomised into the Placebo arm and receive instructions on frequency of administration (daily intake). 40 participants on the control arm are expected to complete the trial.

Acronym Ver-A-T1D
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Masking Description: Trial participants and research teams will be blinded to the treatment group for the duration of the trial. The double blinding will be achieved by providing verapamil SR identical placebo tablets.

Source: ClinicalTrials.gov