TArgeting Type 1 Diabetes Using POLyamines (TADPOL)

Emily K. Sims

Status and phase: Enrolling; Phase 2

Conditions: Type 1 Diabetes

Treatments: Drug: DFMO; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05594563

4-SRA-2022-1205-M-B

Details and patient eligibility

About

The goal of this clinical trial is to test a drug known as DFMO in people with Type 1 Diabetes (T1D). The main question[s] it aims to answer are:

• Does it reduce stress on the cells that make insulin?
• Does it preserve what is left of the body's insulin production? Participants will take either DFMO or a placebo (looks like DFMO but has no active ingredients) two times a day for about 6 months. Participants will have 6 in person visits and 1 phone visit over a period of 12 months. Visits will include blood draws urine collection and other tests.

Full description

This study will be a multicenter, double-blind, placebo-controlled, 2:1 random assigned, phase II clinical trial for individuals with recent onset type 1 diabetes. The investigators are conducting a double masked placebo-controlled intention to treat study enrolling persons with new onset T1D with documented continued residual C-peptide production. Within 45 days of screening and a run-in period during which eligibility will be determined and glycemic control optimized, subjects will have a 6-month double-masked treatment period with either DFMO or placebo. After a 6-month wash-out period the durability of effect will be assessed. Subjects will be randomly assigned either 1000mg/m2/day oral DFMO or placebo treatment at a 2:1 ratio.

Enrollment: 70 estimated patients

Sex: All

Ages: 4 to 40 years old

Volunteers: No Healthy Volunteers

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 frequencies 250, 500, 1000, and 2000 Hz

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

70 participants in 2 patient groups, including a placebo group

Treatment Arm

Active Comparator group

Description:

Difluoromethylornithine (DFMO) pill ,1000mg/m2/day, for 6 months

Treatment:

Drug: DFMO

Placebo Arm

Placebo Comparator group

Description:

Placebo pill taken twice a day orally for 6 months

Treatment:

Drug: Placebo