Clinical trial NCT05847413: Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D
Official title: Targeting Beta Cell Dysfunction With Verapamil in Longstanding T1D
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Benaroya Research Institute
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label proof of concept study
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL at 12 weeks.
timeFrame: 0-12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
Study officials:
affiliation: Benaroya Research Institute
name: Carla Greenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: