Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D

NCT05847413 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB20042
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL at 12 weeks.

  0-12 weeks

Study Arms (1)

Targeting Beta cell Dysfunction with Verapamil in Longstanding T1D

EXPERIMENTAL

Participants will receive verapamil for 12 weeks

Drug: Verapamil

Interventions

Verapamil DRUG

Subjects will receive oral verapamil for 12 weeks

Targeting Beta cell Dysfunction with Verapamil in Longstanding T1D

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ≥ 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%

You may not qualify if:

• 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).

Sponsors & Collaborators

• Benaroya Research Institute: lead

Study Sites (1)

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• Lord SM, Bahnson HT, Greenbaum CJ, Liljenquist DR, Virostko J, Speake C. Testing a new platform to screen disease-modifying therapy in type 1 diabetes. PLoS One. 2023 Dec 14;18(12):e0293268. doi: 10.1371/journal.pone.0293268. eCollection 2023.

  PMID: 38096190 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Verapamil

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Carla Greenbaum, MD

  Benaroya Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label proof of concept study

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 6, 2023
• Study Start: May 30, 2020
• Primary Completion: December 10, 2021
• Study Completion: December 10, 2021
• Last Updated: May 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)