Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes

NCT02372253 | Completed Phase 2 Results

• 1 other identifier: 3-SRA-2014-302-M-R
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The overall purpose of this trial is to assess the efficacy and safety of using oral verapamil in subjects with recent onset T1D in order to downregulate TXNIP and enhance the patients' endogenous beta cell mass and insulin production. The objectives are therefore to assess parameters of beta cell survival (including new biomarkers), insulin production and glucose control and the feasibility of this approach and thereby provide the basis for future, larger/expanded, longer-term verapamil studies and the off-label use of this approved drug for Type 1 Diabetes (T1D).

Conditions

Type 1 Diabetes Mellitus

Keywords

verapamil; type 1 diabetes; diabetes; beta cells; beta cell function; insulin

Outcome Measures

Primary Outcomes (1)

• Functional Beta Cell Mass

  Functional Beta Cell Mass as determined by the area under the curve (AUC) from a 2-hour Mixed Meal-Stimulated C-peptide after daily verapamil for 12 months. A greater improvement in insulin production (as an indirect measure of beta cell mass) in subjects receiving verapamil as compared to those receiving placebo would provide an indication of the efficacy of this intervention. The C-peptide AUC (0-120 min) was calculated by using the trapezoidal rule and was divided by the time of the test to obtain the mean AUC (in nmol/L).

  12 months

Secondary Outcomes (5)

• Percent Change From Baseline in Exogenous Insulin Requirements

  12 months

• Percent Change From Baseline in Exogenous Insulin Requirements

  12 weeks

• HbA1C

  12 months

• HbA1c

  12 weeks

• Hypoglycemic Events

  12 months

Other Outcomes (1)

• Beta Cell Markers

  12 weeks and 12 months

Study Arms (2)

Verapamil

EXPERIMENTAL

13-26 subjects with Type 1 Diabetes meeting the inclusion criteria will be randomly assigned to receive daily oral verapamil for 12 months. The initial dose of verapamil will be 120 mg daily, and this will be advanced if tolerated to a maximum dose of 360 mg daily. The verapamil tablets will be encapsulated to match the placebo capsules

Drug: Verapamil

Placebo

PLACEBO COMPARATOR

13-26 subjects with Type 1 Diabetes meeting the inclusion criteria will be randomly assigned to receive daily oral placebo for 12 months. The initial dose of placebo will be 120 mg daily, and this will be advanced if tolerated to a maximum dose of 360 mg daily. The placebo tablets will be encapsulated to match the verapamil capsules

Drug: Placebo

Interventions

Verapamil DRUG

Verapamil

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must meet all of the following criteria:
• Diagnosis of Type 1a Diabetes Mellitus based on American Diabetes Association (ADA) Criteria
• Written informed consent obtained from the subject including consent for the use of research-related health information
• ≥ 18 years of age and ≤ 45 years of age
• \< 3 months since T1D was diagnosed
• BMI \< 30
• Baseline A1c \<10%
• Detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay)
• C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL
• Presence of antibodies to at least one of the following antigens: insulin, glutamic acid decarboxylase (GAD)-65, Insulinoma Antigen 2 (IA-2) and Zinc Transporter 8 (ZnT8)
• Agree to intensive management of diabetes with a HgbA1c goal of \< 7.0% and willing to wear and insulin pump and Continuous Glucose Monitoring System (CGMS)
• If female, (a) surgically sterile or (b) postmenopausal or (c) if of reproductive potential, willing to use medically acceptable birth control (e.g. female hormonal contraception, barrier methods or sterilization) until 3 months after completion of any Treatment Period
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Currently receiving insulin therapy
• Willing to forego other forms of experimental treatment during the study

You may not qualify if:

• Subjects must have none of the following:
• Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
• Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
• Current therapy with Glucagon-like peptide (GLP)-1 receptor agonists, pramlintide, or any other agents that might be thought to potentially stimulate pancreatic beta cell regeneration or insulin secretion
• Current treatment with oral antidiabetic agents
• 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
• History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease
• Untreated hypothyroidism or active Graves' disease with hyperthyroidism
• Treatment with systemic glucocorticoid therapy by oral, intravenous (IV), or intramuscular (IM) route within 12 weeks before randomization; patients who are likely to require treatment with corticosteroids during the trial are also excluded
• Evidence of active infection
• Total bilirubin \> 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5 x ULN
• A psychiatric or medical disorder that would prevent giving informed consent
• Hypersensitivity to verapamil or any component of the formulation; known left ventricular dysfunction; 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)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Insulin Resistance

Interventions

Verapamil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Anath Shalev, MD
• Organization: UNIVERSITY OF ALABAMA AT BIRMINGHAM

shalev@uab.edu

205-996-4777

Study Officials

• Fernando Ovalle, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Anath Shalev, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 20, 2015
• First Posted: February 26, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2019
• Last Updated: February 5, 2020
• Results First Posted: January 30, 2019

Record last verified: 2019-01

Locations

US (1)