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TArgeting Type 1 Diabetes Using POLyamines (TADPOL)
NCT05594563 · Indiana University
In plain English
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Official title
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
About this study
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.
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 forall 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.
Study design
Enrollment target: 70 participants
Allocation: randomized
Masking: triple
Age groups: child, adult
Timeline
Starts: 2023-03-14
Estimated completion: 2028-05
Last updated: 2025-09-23
Interventions
Drug: DFMODrug: Placebo
Primary outcomes
- • Clinical efficacy of 1000 mg/m2/day of oral DFMO after 6 months of treatment (6 month)
- • Number of participants with treatment-related adverse events as assessed by CTCAE v5 (through study completion, an average of one year)
Sponsor
Emily K. Sims · other
With: Juvenile Diabetes Research Foundation, Cancer Prevention Pharmaceuticals, Inc.
Contacts & investigators
ContactMaria L Spall, BSN · contact · malnicho@iu.edu · 317-278-7034
ContactOperations Manager · contact · tadpol@iu.edu · 317-278-8879
InvestigatorEmily K Sims, MD,MS · study_chair, Indiana University School of Medicine
All locations (7)
Barbara Davis CenterRecruiting
Aurora, Colorado, United States
University of ChicagoRecruiting
Chicago, Illinois, United States
IU Health Riley Hospital for ChildrenRecruiting
Indianapolis, Indiana, United States
Children's Mercy HospitalRecruiting
Kansas City, Kansas, United States
University of MichiganRecruiting
Ann Arbor, Michigan, United States
MHealth Fairview Masonic Children's Hospital and Specialty ClinicsRecruiting
Minneapolis, Minnesota, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States