Verapamil SR in Adults With Type 1 Diabetes

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.

Inclusion criteria

• Have given written informed consent
• Age ≥18 and <45 at consent
• Must have a diagnosis of T1D of within 6 weeks duration at screening (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

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
• 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