ATG + Verapamil for Type 1 Diabetes

Recruiting at 1 trial location

Overseen By Jennifer L Hosford, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: Immunodeficiency, Pregnancy, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for individuals recently diagnosed with type 1 diabetes, using two treatments: Anti-thymocyte globulin (ATG), which targets specific immune cells, and verapamil, a medication that may protect insulin-producing cells. The researchers aim to determine if these treatments can work together to help the body continue producing its own insulin for a longer period. The trial seeks participants diagnosed with type 1 diabetes within the last 100 days who are prepared to manage their diabetes closely. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot use non-insulin drugs that affect blood sugar control within 7 days before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that low-dose anti-thymocyte globulin (ATG) holds promise for treating type 1 diabetes. Research indicates that ATG is generally safe for children and teenagers with newly diagnosed diabetes. Although some side effects can occur, studies suggest that patients usually tolerate ATG well.

For verapamil, studies have demonstrated its general safety and tolerability in young people with newly diagnosed type 1 diabetes. Negative side effects have been rare. Verapamil has also helped maintain pancreatic function.

Overall, both treatments have demonstrated good safety records in past trials. However, monitoring remains important to ensure safety for each individual. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the new approach to treating Type 1 Diabetes with Anti-thymocyte globulin (ATG) and verapamil because these treatments offer unique mechanisms of action compared to standard options like insulin therapy. Unlike insulin, ATG works by modulating the immune system, specifically targeting T cells that contribute to the autoimmune attack on pancreatic beta cells. Verapamil, on the other hand, is a calcium channel blocker traditionally used for heart conditions, which has shown promise in preserving beta cell function by reducing cell stress. This potential dual-action strategy not only aims to control blood sugar levels but also addresses the underlying autoimmune process, offering hope for more comprehensive management of Type 1 Diabetes.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

Research has shown that anti-thymocyte globulin (ATG), which participants in this trial may receive, can protect the cells that produce insulin and improve health outcomes for people newly diagnosed with type 1 diabetes. Studies found that small doses of ATG helped maintain steady insulin production, crucial for controlling blood sugar levels. However, not everyone benefited from ATG, so identifying those most likely to respond well to this treatment is important.

Verapamil, another treatment option in this trial, is a calcium channel blocker. It has also been shown to help maintain insulin production in type 1 diabetes. Verapamil can lower blood sugar levels and support the cells that make insulin. This trial will explore the effectiveness of using these treatments separately, as they address different aspects of the condition, offering a more comprehensive way to manage type 1 diabetes. ^{3 5 6 7 8}

Who Is on the Research Team?

Laura M Jacobsen, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for individuals recently diagnosed with type 1 diabetes. It aims to find out if low doses of ATG can help control blood sugar and preserve insulin production. Participants should likely respond to ATG, as determined by a specific biomarker test.

Inclusion Criteria

I am between 6 and 35 years old.

Be willing to comply with intensive diabetes management

It has been over 6 weeks since my last live vaccine.

Exclusion Criteria

Have evidence of current or past HIV, Hepatitis B or Hepatitis C infection

Be currently pregnant or lactating, or anticipate getting pregnant within the two-year study period

Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-dose ATG or placebo for 1 year to assess C-peptide levels

12 months

Open-label extension

Participants are re-randomized to receive verapamil or not for an additional year to explore mechanistic endpoints

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-thymocyte globulin (ATG)
• Verapamil

Trial Overview The study tests the effectiveness of anti-thymocyte globulin (ATG) alone or followed by verapamil in preserving insulin production in type 1 diabetes patients. It also explores whether combining these treatments has synergistic effects.

How Is the Trial Designed?

Group I: verapamil extended release capsule Experimental Treatment 1 Intervention

Open label administration at 120, 240 or 360 mg daily based on weight and ECG findings

Group II: Anti-thymocyte globulin (ATG) intravenous infusion Experimental Treatment 1 Intervention

ATG (brand name Thymoglobulin) a polyclonal T cell antibody preparation. It will be given at low doses (0.5 mg/kg Day 1 then 2 mg/kg Day 2).

Group III: Placebo-ATG Placebo Group 1 Intervention

Saline placebo

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

Published Research Related to This Trial

In a phase 2 clinical trial involving 58 participants with recent-onset type 1 diabetes, treatment with antithymocyte globulin (ATG) did not preserve β-cell function compared to placebo after 12 months, indicating it may not be an effective treatment for this condition.

While ATG treatment led to significant T-cell depletion and associated adverse events, it did not result in a difference in the incidence of infections between the ATG and placebo groups, suggesting that the safety profile may be concerning due to the high rate of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Gitelman, SE., Gottlieb, PA., Rigby, MR., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12074605/

Therapeutic potential of anti-thymocyte globulin in type 1 ... Results indicated that ATG showed potential in preserving beta-cell function and improving clinical outcomes in recent-onset T1D.

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01773-8/fulltext?rss=yes

ATG as disease-modifying therapy for new-onset type 1 ... The results of the MELD-ATG trial suggest that further studies with ATG are warranted, and remind the field that small dose-finding trials can ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625016745

Minimum effective low dose of antithymocyte globulin in ... In young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential of an affordable ...

4. diabetesjournals.org diabetesjournals.org/care/article/47/2/285/154034/Low-Dose-Antithymocyte-Globulin-A-Pragmatic

Low-Dose Antithymocyte Globulin: A Pragmatic Approach to ... Three subjects (50%) remained diabetes free after 1.5, 3, and 4 years of follow-up, while three developed stage 3 within 1–2 months after ...

5. breakthrought1d.org breakthrought1d.org/for-the-media/press-releases/breakthrough-t1d-encouraged-by-results-of-clinical-trial-demonstrating-effectiveness-of-existing-drug-in-new-onset-type-1-diabetes/

Breakthrough T1D Encouraged by Results of Clinical Trial ... This study, using an adaptive trial design, successfully tested a range of low doses of ATG and identified a minimum effective low dose that ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6489466/

Antithymocyte globulin treatment for patients with recent-onset ... We assessed the safety and efficacy of rabbit ATG in preserving islet function in participants with recent-onset type 1 diabetes, and report here our 12-month ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02215200

NCT02215200 | ATG-GCSF in New Onset Type 1 Diabetes This is a three-arm, 1:1:1 randomized, placebo controlled, double- blinded trial in which at least 28 subjects will receive active Anti-Thymocyte Globulin ...

8. diabetesjournals.org diabetesjournals.org/care/article/41/9/1917/40730/Low-Dose-Anti-Thymocyte-Globulin-ATG-Preserves

Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell ... A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in 89 subjects: 29 ...