Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D

Study Overview
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Brief Summary
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The purpose of this study is to determine whether verapamil can transiently improve beta cell function in those who do or do not secrete proinsulin and little/no C-peptide.

Official Title
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Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Verapamil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 3 years from Type 1 diabetes diagnosis Males and females 18-50 years of age, inclusive Peak MMTT stimulated C-peptide < 0.017 pmol/mL Females of child-bearing potential must be willing to use effective birth control for 12 weeks Willing and able to give informed consent for participation HbA1c ≤ 8.5% Exclusion Criteria: Concurrent use of non-insulin therapies aimed to control hyperglycemia or use within the past 30 days of initial qualifying MMTT (V-2). 2. Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT or AST> 1.5 x the upper limit of age-determined normal (ULN). 3. Renal disease, as defined by creatinine ≥1.5 mg/dL. 4. Hypersensitivity to verapamil or any component of the formulation. 5. Previous use of verapamil. 6. Known left ventricular dysfunction; bradycardia (HR <50 BPM) 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) 7. 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. 8. Use of beta blockers or medium-high dose statins: any dose of atorvastatin (Lipitor) or rosuvastatin (Crestor); simvastatin > 10 mg daily; lovastatin > 20 mg; pravastatin > 20 mg 9. Use of other medications which may increase the concurrent risk of verapamil use, including medications which utilize the cytochrome p450 enzyme pathway. 10. Females who are pregnant or lactating. 11. Receipt of an immune modulating biologic or investigational drug within 3 months or 5 half-lives before enrollment. 12. History of other clinically significant autoimmune disease except for celiac and stable thyroid disease. 13. Current use of any medication known to significantly influence glucose tolerance (e.g. oral steroids, atypical antipsychotics, diphenylhydantoin, niacin). 14. Any medical or psychological condition that in the opinion of the principal investigator would interfere with the safe completion of the trial. Conditions to consider include history of chronic GERD, chronic constipation, and chronic nausea. 15. Specific to MRI subjects: non-removable ferromagnetic materials or MRI not technically feasible (claustrophobia, movement disorder, obesity).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: open label proof of concept study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Targeting Beta cell Dysfunction with Verapamil in Longstanding T1D<br>Participants will receive verapamil for 12 weeks | Drug: Verapamil<br>* Subjects will receive oral verapamil for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL at 12 weeks. |  | 0-12 weeks |