Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Verapamil

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 3 years from Type 1 diabetes diagnosis
2. Males and females 18-50 years of age, inclusive
3. Peak MMTT stimulated C-peptide < 0.017 pmol/mL
4. Females of child-bearing potential must be willing to use effective birth control for 12 weeks
5. Willing and able to give informed consent for participation
6. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Targeting Beta cell Dysfunction with Verapamil in Longstanding T1D; Participants will receive verapamil for 12 weeks	Drug: Verapamil; Subjects will receive oral verapamil for 12 weeks

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Benaroya Research Institute
• Investigators: Principal Investigator: Carla Greenbaum, MD, Benaroya Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2020
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): December 10, 2021

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Estimate): May 8, 2023

Study Record Updates

• Last Update Posted (Estimate): May 8, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Verapamil
• Other Study ID Numbers: IRB20042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No