Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02372253|
Recruitment Status : Completed
First Posted : February 26, 2015
Results First Posted : January 30, 2019
Last Update Posted : February 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Drug: Verapamil Drug: Placebo||Phase 2|
Loss of pancreatic beta-cell mass is a key factor in T1D, but therapies to halt this process are not available. The investigators have discovered thioredoxin-interacting protein (TXNIP), as a promising target in this regard and have now found that the commonly used anti-hypertensive drug and calcium channel-blocker, verapamil, effectively lowers beta-cell TXNIP expression in rodent beta-cells and human islets, promotes beta-cell survival and rescues mice from T1D. This makes verapamil a potentially attractive drug for T1D, but prospective clinical data are lacking. The investigators primary objective is therefore to conduct a randomized, placebo-controlled, double-blind study of the efficacy and safety of verapamil in adults with recent-onset T1D and to demonstrate that subjects on oral verapamil daily for 12 months will have improved insulin production (as an indirect measure of beta-cell mass).
Results will have major translational implications with potential immediate impact on clinical care, encourage large clinical follow-up trials, evaluate markers of beta cell health and ultimately help develop a novel therapy that enhances the patient's own beta-cell mass and function.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Repurposing of Verapamil as a Beta Cell Survival Therapy in Type 1 Diabetes|
|Study Start Date :||February 2015|
|Actual Primary Completion Date :||December 2017|
|Actual Study Completion Date :||December 2019|
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
Placebo Comparator: Placebo
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
- Functional Beta Cell Mass [ Time Frame: 12 months ]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).
- Percent Change From Baseline in Exogenous Insulin Requirements [ Time Frame: 12 months ]Percent change in exogenous insulin requirements over the last 7-14 consecutive days at 12 months. This will be assessed as a surrogate inverse marker of residual beta cell function.
- Percent Change From Baseline in Exogenous Insulin Requirements [ Time Frame: 12 weeks ]Percent change in exogenous insulin requirements over the last 7-14 consecutive days at 12 weeks. This will be assessed as a surrogate inverse marker of residual beta cell function.
- HbA1C [ Time Frame: 12 months ]Glycemic control, as measured by HbA1c. In addition to being an important determinant of residual beta cell function/survival, it also helps reveal a more complete picture of beta cell function.
- HbA1c [ Time Frame: 12 weeks ]Glycemic control, as measured by HbA1c. In addition to being an important determinant of residual beta cell function/survival, it also helps reveal a more complete picture of beta cell function.
- Hypoglycemic Events [ Time Frame: 12 months ]Glycemic control, as measured by hypoglycemic events.
- Beta Cell Markers [ Time Frame: 12 weeks and 12 months ]Beta cell markers. We will collect serum at baseline and at Week 12 and Months 6, 9 and 12 for future assessment of putative beta cell markers.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02372253
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35233|
|Principal Investigator:||Fernando Ovalle, MD||University of Alabama at Birmingham|
|Principal Investigator:||Anath Shalev, MD||University of Alabama at Birmingham|