Testing a drug to help preserve insulin production in Type 1 Diabetes

TArgeting Type 1 Diabetes Using POLyamines (TADPOL): A Randomized, Double-Masked, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Difluoromethylornithine (DFMO) to Preserve Insulin Production in Type 1 Diabetes

This study is testing if a drug called DFMO can help people with newly diagnosed Type 1 Diabetes keep their insulin-producing cells healthy and working longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 81 (estimated)
• Ages: 4 Years to 40 Years
• Sex: All
• Sponsor: Indiana University (Academic / other)
• Locations: 7 sites (Aurora, Colorado and 6 other locations)
• Trial ID: NCT05594563 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of a drug called DFMO in individuals with recent onset Type 1 Diabetes (T1D). Participants will be randomly assigned to receive either DFMO or a placebo for a duration of six months, with the goal of assessing whether DFMO can reduce stress on insulin-producing cells and preserve remaining insulin production. The study will involve multiple in-person visits for blood draws, urine collection, and other tests over a 12-month period, including a wash-out phase to evaluate the durability of any effects observed. The trial is designed as a multicenter, double-blind, placebo-controlled study to ensure robust results.

Who should consider this trial

Good fit: Ideal candidates include males and females aged 4 to 40 years with a recent diagnosis of Type 1 Diabetes and detectable residual insulin production.

Not a fit: Patients with diabetes types other than Type 1 or those with severe, active diseases that interfere with dietary intake may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could help maintain insulin production in patients with Type 1 Diabetes, potentially improving their management of the condition.

How similar studies have performed: While this approach is novel in its specific application, similar studies targeting insulin preservation in Type 1 Diabetes have shown promise.

Eligibility criteria

Inclusion Criteria:

1. Males and females 4- ≥40 years of age with a clinical diagnosis of T1D
2. T1D clinical diagnosis with insulin start date no more than 100 days prior to the time of randomization
3. Random non-fasting C-peptide level of \>0.2 pmol/mL (equivalent to \>0.6ng/ml) at screening.
4. Positive for any one of the following diabetes-related autoantibodies (IAA, GAA, IA-2, or ZnT8)
5. Treatment naïve of any immunomodulatory agent
6. Normal hearing at screening, defined as acceptable results of pure-tone audiometry (\<20 decibel \[dB\] baseline thresholds for all frequencies tested

Exclusion Criteria:

1. Presence of severe, active disease that interferes with dietary intake or requires the use of chronic medication, with the exception of well-controlled hypothyroidism and mild asthma not requiring oral steroids. Presence of any psychiatric disorder that will affect ability to participate in study.
2. Diabetes other than T1D
3. Chronic illness known to affect glucose metabolism (e.g. Cushing syndrome, polycystic ovarian disorder, cystic fibrosis) or taking medications that affect glucose metabolism (e.g. steroids, metformin)
4. Inability to swallow pills
5. Psychiatric impairment or current use of anti-psychotic medication
6. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
7. Neutropenia (\< 1,500 neutrophils/μL)
8. Leukopenia (\< 3,000 leukocytes /μL)
9. Lymphopenia ( \< 800 lymphocytes/μL)
10. Thrombocytopenia (\<100,000 platelets/μL)
11. Clinically significant anemia or Hemoglobin as defined below:

    In Adults: Hgb \<12.0g/dL in females and \<13.0g/dL in males In Children: 12- \<18: \<11.4 g/dL in females and \<12.4 g/dL in males In Children: 4- \<12: Hgb \<11.2 g/dL
12. Impaired renal function (assessed by history and BUN/Creatinine, DFMO is renally excreted)
13. Allergy to milk or soy (components of Boost® drink used for mixed meal tolerance testing)
14. Female participants of child-bearing age with reproductive potential, must not be pregnant and agree to use 2 effective forms of birth control or be abstinent during the study period (see below). Male participants (including men who have had vasectomies) whose partners are pregnant or may be pregnant should use condoms while on study drug, until 2 weeks after discontinuation of drug, while the partner is pregnant.
15. Active seizure disorder, defined as requiring chronic medication at the time of study or having had a seizure within the past 12 months at the time of screening
16. Enrollment into another intervention trial.
17. Use of an automated insulin delivery system, including hybrid closed loop or fully closed loop insulin pumps) that do not allow for manual suspension or temporary modification of insulin delivery for bolus dosing.

Where this trial is running

Aurora, Colorado and 6 other locations

• Barbara Davis Center — Aurora, Colorado, United States (Recruiting)
• University of Chicago — Chicago, Illinois, United States (Recruiting)
• IU Health Riley Hospital for Children — Indianapolis, Indiana, United States (Recruiting)
• Children's Mercy Hospital — Kansas City, Kansas, United States (Recruiting)
• University of Michigan — Ann Arbor, Michigan, United States (Recruiting)
• MHealth Fairview Masonic Children's Hospital and Specialty Clinics — Minneapolis, Minnesota, United States (Recruiting)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Study coordinator: Maria L Spall, BSN

Conditions Type 1 Diabetes