Clinical trial NCT05594563: TArgeting Type 1 Diabetes Using POLyamines (TADPOL)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Type 1 Diabetes
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
name: Cancer Prevention Pharmaceuticals, Inc.
First posted: 2022-10-26
Enrollment: 70
Sex: ALL
Minimum age (years): 4
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subject are randomized to either treatment or placebo arm.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

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.

Primary outcomes:
measure: Clinical efficacy of 1000 mg/m2/day of oral DFMO after 6 months of treatment
timeFrame: 6 month
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5
timeFrame: through study completion, an average of one year
Secondary outcomes:
measure: Clinical efficacy of 1000 mg/m2/day of oral DFMO after 3 months of treatment, 9 months after treatment (or 3 months after treatment end), and 12 months after treatment (or 6 months after treatment end).
timeFrame: through study completion, an average of one year
measure: Decrease in urinary polyamides after 6 months of DFMO treatment.
timeFrame: up to 24 weeks after treatment
measure: Biomarkers of β cell stress at 3, 6, 9, and 12 months after treatment.
timeFrame: through study completion, an average of one year
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Riley Hospital for Children
state: Indiana
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Indiana University School of Medicine
name: Emily K Sims, MD,MS
role: STUDY_CHAIR
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