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Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Verapamil
Sponsored by
Benaroya Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 1 Diabetes

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Benaroya Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Targeting Beta cell Dysfunction with Verapamil in Longstanding T1D

Arm Description

Participants will receive verapamil for 12 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
April 27, 2023
Last Updated
April 27, 2023
Sponsor
Benaroya Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05847413
Brief Title
Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D
Official Title
Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
May 30, 2020 (Actual)
Primary Completion Date
December 10, 2021 (Actual)
Study Completion Date
December 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Benaroya Research Institute

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
open label proof of concept study
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Targeting Beta cell Dysfunction with Verapamil in Longstanding T1D
Arm Type
Experimental
Arm Description
Participants will receive verapamil for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Verapamil
Intervention Description
Subjects will receive oral verapamil for 12 weeks
Primary Outcome Measure Information:
Title
Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL at 12 weeks.
Time Frame
0-12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carla Greenbaum, MD
Organizational Affiliation
Benaroya Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Benaroya Research Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D

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