Verapamil SR in Adults With Type 1 Diabetes
- Conditions
- Diabetes Mellitus, Type 1
- Interventions
- Drug: Placebo
- Registration Number
- NCT04545151
- Lead Sponsor
- 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 31 academic institutions, 6 industrial partners, a small sized enterprise and 2 patient organizations, 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 138
- 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: GADA, IA-2A and/or ZnT8A
- Must have fasting C-peptide levels ≥100 pmol/L measured at screening
- Be willing to comply with intensive diabetes management
- 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
- 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
- History of renal insufficiency or 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 its excipients
- Concomitant medication known for significantly inducing or inhibiting CYP3A4 and/or glycoprotein-P metabolism
- Intake of grapefruit juice, licorice, St.John's Wort, cannabidiol, ginkgo biloba
- Substrate intake of CYP3A4 and/or glycoprotein-P metabolism, as judged by the investigator
- 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)
- ECG second or third degree atrioventricular block; Incomplete branch block
- Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
- Current use of ß-blockers
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Verapamil SR Verapamil SR 120 mg 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. Placebo Placebo 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.
- Primary Outcome Measures
Name Time Method Area under the stimulated C-peptide response curve At 12 months The primary objective is 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 Outcome Measures
Name Time Method Area under the stimulated C-peptide response curve At 3, 6, 9 and 24 months The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT)
Fasting C-peptide At 12 months 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.
Proinsulin, Insulin, Pro-IAPP and Proglucagon secretion At baseline and 3, 6, 9 and 12 months Proinsulin, Insulin, Pro-IAPP and Proglucagon secretion during the first two hours of a mixed meal tolerance test (MMTT)
DBS C-peptide At baseline, week 4, week 8, and 3, 6, and 9 months The DBS (Dried blood spot) C-peptide measurements at all observation times
Change in HbA1c Baseline, 12 and 24 months 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.
Severe hypoglycaemic episodes Baseline to 12 months 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)
DKA Baseline to 12 months Number of treatment emergent episodes of diabetic ketoacidosis
Change in insulin requirements Baseline, 12 and 24 months Change in insulin requirements, baseline to 12 months as the daily total dose (three days average) in units per kg body weight (BW)
Change in T1D associated autoantibodies Baseline to 12 months Change in T1D associated autoantibodies (GADA, IAA, IA-2A and ZnT8A) from 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) Continous glucose monitoring (CGM) time in range (70-140 mg/dL, 3.9-7.8 mmol/L) and (70-180 mg/dL, 3.9-10.0 mmol/L), time above range (\>180 mg/dL, \>10.0 mmol/L), time below range (\<70 mg/dL, \< 3.9 mmol/L)
Trial Locations
- Locations (22)
Medical University of Graz, Department of Internal Medicine Division of Endocrinology and Metabolism
🇦🇹Graz, Styria, Austria
Universitair Ziekenhuis Brussel
🇧🇪Brussels, Belgium
Université Libre de Bruxelles/ Hôpital Erasme
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Katholieke Universiteit Leuven
🇧🇪Leuven, Belgium
Institut National de la Santé et de la Recherche Médicale
🇫🇷Paris, France
HKA Hannover
🇩🇪Hanover, Germany
Universität Ulm
🇩🇪Ulm, Germany
Università Vita-Salute San Raffaele
🇮🇹Milano, Italy
Università degli Studi di Siena
🇮🇹Siena, Italy
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Southmead Hospital
🇬🇧Bristol, United Kingdom
Addenbrokes Hospital
🇬🇧Cambridge, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
NHS Greater Glasgow and Clyde-Queen Elizabeth University Hospital, Department of Diabetes
🇬🇧Glasgow, United Kingdom
Bart's Hospital QMUL
🇬🇧London, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
Queens Medical Centre
🇬🇧Nottingham, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
OCDEM, John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Singleton Hospital
🇬🇧Swansea, United Kingdom