Adalimumab + Verapamil for Type 1 Diabetes

(WAVE T1D Trial)

Not yet recruiting at 10 trial locations

Overseen By Robert Henderson, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunomodulators, Teplizumab, Beta blockers, others

Disqualifiers: Infections, Cardiac disease, Immunodeficient, others

Compensation: Varies

Number of Visits: Unknown

Duration: 156 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatments, adalimumab and verapamil, to determine if they help preserve insulin production in individuals with newly diagnosed Type 1 Diabetes. The primary goal is to assess whether these treatments can maintain pancreatic function over two years while ensuring safety. Participants will first receive Anti-thymocyte Globulin (ATG), followed by either adalimumab, verapamil, or a placebo. The trial seeks individuals diagnosed with Type 1 Diabetes within the last six months who are committed to closely managing their condition. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires participants to stop using any non-insulin glucose-lowering agents at least 30 days before screening and throughout the study. Additionally, certain medications like beta blockers, seizure medications, and some antihypertensive drugs are not allowed during the study.

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

Research has shown that ATG (anti-thymocyte globulin) has been tested in people with type 1 diabetes and appears safe over one to two years. Studies suggest it can help maintain certain cell functions without major safety issues.

When combined with adalimumab, ATG improved outcomes in people with newly diagnosed type 1 diabetes. Although specific side effects aren't listed, the treatment is generally considered safe.

For ATG combined with verapamil, research indicates that verapamil is safe for children and teenagers with newly diagnosed diabetes. It also helped maintain some insulin production over a year.

Overall, these treatments have been studied for their potential benefits in type 1 diabetes and are generally well-tolerated, though specific side effects may vary for each combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Type 1 Diabetes focus on managing blood sugar levels, often using insulin therapy. However, the combination of Adalimumab and Verapamil is exciting because it targets the immune system, which plays a role in the progression of Type 1 Diabetes. Adalimumab is an anti-inflammatory drug that may help protect insulin-producing cells, while Verapamil is typically used for blood pressure control but has shown promise in preserving beta-cell function. This dual approach could potentially modify the disease course, offering more than just symptom management. Researchers are eager to see if these treatments can effectively slow down or alter the disease, which would be a significant leap forward from current options.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

Research shows that Anti-thymocyte Globulin (ATG) may protect the cells that produce insulin in individuals who have recently developed type 1 diabetes. Studies have found that a low dose of ATG can maintain C-peptide levels, indicating preserved insulin production, and can also lower HbA1c, which measures blood sugar levels. In this trial, one group of participants will receive ATG combined with adalimumab, a treatment that reduces inflammation and might enhance these benefits, potentially leading to better health outcomes. Another group will receive ATG combined with verapamil, which research has shown can stabilize blood sugar levels and support insulin production. Both treatment combinations aim to reduce the immune system's attack on insulin-producing cells, crucial for managing type 1 diabetes. ^{1 2 4 6 7}

Who Is on the Research Team?

Alberto Pugliese, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals aged 9 to <21 who have been recently diagnosed with stage 3 Type 1 Diabetes. The full eligibility criteria are not provided, so interested participants should inquire further for inclusion and exclusion details.

Inclusion Criteria

Women of childbearing potential (WOCBP) must use an acceptable form of birth control

I am a man who can father children and agree to use birth control or abstain from sex during the study.

Must have been vaccinated for flu (if currently in flu season)

Exclusion Criteria

Leukocytosis (>14,000/mL)

Have evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON), or a positive test for latent tuberculosis

Have positive COVID-19 self-antigen test within 3 days of randomization

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 followed by either adalimumab or verapamil. ATG is administered on Day 1 and Day 2, followed by adalimumab injections every other week or daily oral verapamil from the 6-week visit until the 156-week visit.

156 weeks

Bi-weekly visits for adalimumab group, daily administration for verapamil group

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at various time points including week 13, week 26, week 52, week 78, and week 104.

104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab
• Anti-thymocyte Globulin (ATG)
• Verapamil

Trial Overview The trial is testing the safety and effectiveness of Anti-thymocyte Globulin (ATG) followed by either Adalimumab or Verapamil in preserving insulin production in young people with new-onset Type 1 Diabetes over a period of two years.

How Is the Trial Designed?

Group I: ATG + Verapamil Experimental Treatment 1 Intervention

Low dose ATG (0.5 mg/kg Day 1 then 2 mg/kg Day 2). From the 6-week visit until the 156-week visit, daily oral administration at 60, 120, 240 or 360 mg based on weight and ECG findings.

Group II: ATG + Adalimumab Experimental Treatment 1 Intervention

Low dose ATG (0.5 mg/kg Day 1 then 2 mg/kg Day 2). From the 6-week visit until the 156-week visit, Participants will receive a 40 mg dose injection every other week.

Group III: ATG + Placebo Placebo Group 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). This group will receive Verapamil (Oral) placebo or Adalimumab (injectable) placebo.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Jaeb Center for Health Research

Collaborator

Trials

162

Recruited

36,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07061574

NCT07061574 | A Randomized Phase 1/2 Trial of Low ... The primary objective of this study is to assess the safety and efficacy of ATG followed by either adalimumab or verapamil in preserving insulin secretion 2 ...

2. 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.

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

Low-Dose Antithymocyte Globulin: A Pragmatic Approach to ... Low-dose antithymocyte globulin (ATG) (2.5 mg/kg) preserves C-peptide and reduces HbA 1c in new-onset stage 3 type 1 diabetes.

4. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(13)70065-2/abstract

Antithymocyte globulin treatment for patients with recent ... 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 ...

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

Antithymocyte globulin treatment for patients with recent-onset ... Findings from preclinical studies and pilot clinical trials suggest that antithymocyte globulin (ATG) might be effective for reducing this autoimmune response.

6. 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 ...

7. link.springer.com link.springer.com/article/10.1007/s00125-016-3917-4

2 year results of a randomised trial | Diabetologia We previously reported the 1-year results of a trial investigating a 4-day course of antithymocyte globulin (ATG) administered to patients with ...