Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Verapamil; Placebo
Intervention MeSH terms: Verapamil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: verapamil; type 1 diabetes; diabetes; beta cells; beta cell function; insulin

Summary:

      The overall purpose of this trial is to assess the efficacy and safety of using oral
      verapamil in subjects with recent onset T1D in order to downregulate TXNIP and enhance the
      patients' endogenous beta cell mass and insulin production. The objectives are therefore to
      assess parameters of beta cell survival (including new biomarkers), insulin production and
      glucose control and the feasibility of this approach and thereby provide the basis for
      future, larger/expanded, longer-term verapamil studies and the off-label use of this approved
      drug for Type 1 Diabetes (T1D).
    

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)