Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes
Type 1 Diabetes Mellitus
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring verapamil, type 1 diabetes, diabetes, beta cells, beta cell function, insulin
Eligibility Criteria
Inclusion Criteria:
- Subjects must meet all of the following criteria:
- Diagnosis of Type 1a Diabetes Mellitus based on American Diabetes Association (ADA) Criteria
- Written informed consent obtained from the subject including consent for the use of research-related health information
- ≥ 18 years of age and ≤ 45 years of age
- < 3 months since T1D was diagnosed
- BMI < 30
- Baseline A1c <10%
- Detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay)
- C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL
- Presence of antibodies to at least one of the following antigens: insulin, glutamic acid decarboxylase (GAD)-65, Insulinoma Antigen 2 (IA-2) and Zinc Transporter 8 (ZnT8)
- Agree to intensive management of diabetes with a HgbA1c goal of < 7.0% and willing to wear and insulin pump and Continuous Glucose Monitoring System (CGMS)
- If female, (a) surgically sterile or (b) postmenopausal or (c) if of reproductive potential, willing to use medically acceptable birth control (e.g. female hormonal contraception, barrier methods or sterilization) until 3 months after completion of any Treatment Period
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Currently receiving insulin therapy
- Willing to forego other forms of experimental treatment during the study
Exclusion Criteria:
- Subjects must have none of the following:
- Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
- Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
- Current therapy with Glucagon-like peptide (GLP)-1 receptor agonists, pramlintide, or any other agents that might be thought to potentially stimulate pancreatic beta cell regeneration or insulin secretion
- Current treatment with oral antidiabetic agents
- Uncompensated heart failure, fluid overload, myocardial infarction or evidence of ischemic heart disease or other serious cardiac disease as described in New York Heart Association (NYHA) Class III or IV criteria within the 12 weeks before randomization
- History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease
- Untreated hypothyroidism or active Graves' disease with hyperthyroidism
- Treatment with systemic glucocorticoid therapy by oral, intravenous (IV), or intramuscular (IM) route within 12 weeks before randomization; patients who are likely to require treatment with corticosteroids during the trial are also excluded
- Evidence of active infection
- Total bilirubin > 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 x ULN
- A psychiatric or medical disorder that would prevent giving informed consent
- Hypersensitivity to verapamil or any component of the formulation; known left ventricular dysfunction; hypotension (systolic pressure <90 mm Hg); PR interval prolongation on EKG or any bradyarrhythmia (e.g. sick sinus syndrome, Anterior Ventral (AV) block); atrial flutter or fibrillation, and an accessory bypass tract (Wolff-Parkinson- White (WPW) syndrome, Lown-Ganong-Levine syndrome)
Sites / Locations
- University of Alabama at Birmingham
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Verapamil
Placebo
13-26 subjects with Type 1 Diabetes meeting the inclusion criteria will be randomly assigned to receive daily oral verapamil for 12 months. The initial dose of verapamil will be 120 mg daily, and this will be advanced if tolerated to a maximum dose of 360 mg daily. The verapamil tablets will be encapsulated to match the placebo capsules
13-26 subjects with Type 1 Diabetes meeting the inclusion criteria will be randomly assigned to receive daily oral placebo for 12 months. The initial dose of placebo will be 120 mg daily, and this will be advanced if tolerated to a maximum dose of 360 mg daily. The placebo tablets will be encapsulated to match the verapamil capsules