DFMO in Children With Type 1 Diabetes

NCT02384889 | Completed Phase 1 DMC

• 1 other identifier: 1411735324
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

This study is a multicenter, double-blind, placebo-controlled, 2:1 randomly assigned, phase 1 clinical trial for individuals with type 1 diabetes. It is a blinded dose-ranging study enrolling patients with new onset type 1 diabetes with documented continued residual C-peptide production. After a 4 week screening and run-in period during which eligibility will be determined and glycemic control optimized, subjects will have a 3-month double-masked treatment period with either DFMO or placebo. After a 3 month wash-out period the durability of effect will be assessed. Subjects will be randomly assigned (6 to DFMO; 3 to placebo in each cohort) to 1 of 4 sequential dose cohorts.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Dose Limiting Toxicities

  Low platelet counts, low white blood cell counts, low hemoglobin, severe abdominal pain/diarrhea, hearing loss

  6 month

Other Outcomes (1)

• Changes in Serum Markers of Beta Cell Stress

  6 months

Study Arms (2)

Difluoromethylornithine

EXPERIMENTAL

Subjects may be given daily dose of DFMO

Drug: Difluoromethylornithine

Placebo

PLACEBO COMPARATOR

Subjects may be given daily dose of placebo

Drug: Placebo

Interventions

Difluoromethylornithine DRUG

Active Therapy with DFMO

Also known as: DFMO

Difluoromethylornithine

Placebo DRUG

Placebo Comparitor

Also known as: Comparitor

Placebo

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females 12-40 years of age with a clinical diagnosis of T1D within 2 - 8 months after diagnosis at the time of visit 2.
• Random non-fasting C-peptide level of \>0.2 pmol/mL at visit 1.
• Positive for any one of the following diabetes-related autoantibodies (mIAA, GADA, IA-2A, or ZnT8A)
• Treatment naïve of any immunomodulatory agent
• 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

You may not qualify if:

• 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.
• Diabetes other than T1D
• 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)
• Inability to swallow pills
• Psychiatric impairment or current use of anti-psychotic medication
• Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
• Hematologic abnormalities at screening (anemia, leukopenia (particularly neutropenia), or thrombocytopenia)
• Impaired renal function (assessed by history and BUN/Creatinine, DFMO is renally excreted)
• Female participants of child-bearing age must not be pregnant and agree to use an effective form of birth control or be abstinent during the study period.
• BMI \>95% for age and sex

Sponsors & Collaborators

• Indiana University: lead

Study Sites (3)

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Women and Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

Children's Hospital of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (2)

• Sims EK, Kulkarni A, Hull A, Woerner SE, Cabrera S, Mastrandrea LD, Hammoud B, Sarkar S, Nakayasu ES, Mastracci TL, Perkins SM, Ouyang F, Webb-Robertson BJ, Enriquez JR, Tersey SA, Evans-Molina C, Long SA, Blanchfield L, Gerner EW, Mirmira RG, DiMeglio LA. Inhibition of polyamine biosynthesis preserves beta cell function in type 1 diabetes. Cell Rep Med. 2023 Nov 21;4(11):101261. doi: 10.1016/j.xcrm.2023.101261. Epub 2023 Nov 1.

  PMID: 37918404 DERIVED

• Robertson MA, Padgett LR, Fine JA, Chopra G, Mastracci TL. Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish. Islets. 2020 Sep 2;12(5):99-107. doi: 10.1080/19382014.2020.1791530. Epub 2020 Jul 25.

  PMID: 32715853 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Eflornithine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 12, 2015
• First Posted: March 10, 2015
• Study Start: April 1, 2015
• Primary Completion: October 7, 2019
• Study Completion: January 6, 2020
• Last Updated: September 5, 2021

Record last verified: 2021-09

Locations

US (3)