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Type 1 Diabetes MellitusPhase 2NCT02372253

Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes

A Phase 2 study testing Verapamil in people with Type 1 Diabetes Mellitus, run by University of Alabama at Birmingham at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Verapamil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
1 siteUnited States
Study dates
Feb 2015to Dec 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

Other trials in United States

About this study

Official title: Repurposing of Verapamil as a Beta Cell Survival Therapy in Type 1 Diabetes

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).

Read the detailed description

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.

Being tested
Verapamil, Placebo
Keywords
verapamil, type 1 diabetes, diabetes, beta cells, beta cell function, insulin
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VerapamilDrug

  • PlaceboDrug

Study groups in NCT02372253
Study groupRoleWhat they receive
VerapamilExperimental13-26 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
Receives: Drug: Verapamil
PlaceboPlacebo comparator13-26 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
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 12 months

Secondary outcomes (5)

  1. Percent Change From Baseline in Exogenous Insulin Requirements

    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.

    Measured: 12 months

  2. Percent Change From Baseline in Exogenous Insulin Requirements

    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.

    Measured: 12 weeks

  3. HbA1C

    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.

    Measured: 12 months

  4. HbA1c

    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.

    Measured: 12 weeks

  5. Hypoglycemic Events

    Glycemic control, as measured by hypoglycemic events.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2015 (estimated)
  2. Study startFeb 2015
  3. Primary completionDec 2017
  4. Study completionDec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02372253
Sponsor's protocol ID
3-SRA-2014-302-M-R
Status last verified
Jan 2019
First submitted
20 Feb 2015
Last updated
5 Feb 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Verapamil in people with Type 1 Diabetes Mellitus, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Functional Beta Cell Mass (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02372253.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.

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