Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02384889 |
Other study ID # |
1411735324 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
April 2015 |
Est. completion date |
January 6, 2020 |
Study information
Verified date |
September 2021 |
Source |
Indiana University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
This study is repurposing alpha difluoromethylornithine (DFMO) in order to characterize its
effects in persons with new onset type 1 diabetes. In preliminary studies in mice, inhibition
of polyamine synthesis with DFMO preserved β-cell insulin production and delayed diabetes
onset. Polyamine modulation has the potential to improve β cell health in persons with T1D.
The investigators propose that decreasing polyamine synthesis in persons with new onset T1D
will improve markers of ß cell health and function.
This double-masked, placebo-controlled dose-finding randomized multiple ascending dose study
will include a 1-month screening period; a 3-month double-masked treatment period; and a
3-month follow-up period. Subjects will be randomly assigned to 1 of 4 sequential dose
cohorts: DFMO at nominal (starting) doses of 125 mg/m2 per day, 250 mg/m2 per day, 500 mg/m2
per day, and then 750 mg/m2 per day. Dose escalation will be done based upon whether any dose
limiting toxicities are observed and whether any suggestion of effect on biomarkers of β-cell
stress is observed. At a maximum dose, the cohort will be expanded in order to estimate
biomarker activity. If there is no suggestion of effect and no dose-limiting toxicity 750
mg/m2 per day, a 750 mg per day group will be enrolled. Regardless of the dose we expand, the
investigators will evaluate efficacy of treatment on the primary and secondary outcomes. The
primary outcome endpoint in this study will be the safety of the doses. In particular, the
dose-limiting toxicities known to be potential side effects of DFMO (thrombocytopenia,
neutropenia, anemia, audiometric impairment) will be reviewed and monitored by an internal
safety review committee before each cohort is enrolled. Secondary outcomes will include
biomarkers of beta cell stress, measures of insulin production/glycemia. Exploratory outcomes
will include flow cytometry assessment of B- and T-cell subsets, quantification of polyamine
intake and excretion, and pharmacokinetic DFMO concentrations. Completion of this study will
facilitate future work in studies of DFMO or other inhibitors of pathways that influence
intracellular polyamine levels, including non-steroidal inflammatory agents, and novel
polyamine transport inhibitors. .