Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus
Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing ß cells. Although exogenous insulin is widely available, it is not possible for affected individuals to consistently achieve euglycemia with current technology, and thus they are at risk for devastating long-term complications. This phase II study is designed to evaluate the safety and efficacy of imatinib mesylate as a novel therapy for new-onset T1DM. Imatinib is a first-in-class tyrosine kinase inhibitor.
This study will explore the potential role of short-term therapy with imatinib to induce tolerance and possibly lead to a durable long-term remission of T1DM.
Diabetes Mellitus, Type I
Diabetes Mellitus, Insulin-Dependent, 1
Type 1 Diabetes Mellitus
Insulin-Dependent Diabetes Mellitus 1
Drug: Imatinib Mesylate
Drug: Placebo (For imatinib mesylate)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-Onset Type 1 Diabetes Mellitus|
- Effect of treatment with imatinib versus placebo in individuals [ Time Frame: Visit 9 (Week 52) ] [ Designated as safety issue: No ]The primary outcome of each participant is the area under the stimulated C-peptide curve (AUC) over the first 2 hours of a 4-hour mixed meal glucose tolerance test conducted at the one-year visit.
- Mean area under the stimulated C-peptide curve (AUC) curve at 12 months [ Time Frame: Visit 9 (Week 52) ] [ Designated as safety issue: No ]MMTT-stimulated peak and 4 hour C-peptide AUC at weeks 52
- Mean area under the stimulated C-peptide curve (AUC) over 4 hours at 24 months [ Time Frame: Visit 13 (Week 104) ] [ Designated as safety issue: No ]MMTT-stimulated peak, 2 hour C-peptide, and 4 hour C-peptide AUC at week 104.
- Change in HbA1c levels over time [ Time Frame: Visit 9 (Week 52) and Visit 13 (Week 104) ] [ Designated as safety issue: No ]
- Change in Insulin dose (units/kg) over time [ Time Frame: Visit 9 (Week 52) and Visit 13 (Week 104) ] [ Designated as safety issue: No ]Assess insulin use in units per kilogram body weight per day at weeks 52 and 104.
- Number of severe hypoglycemic events [ Time Frame: Visit 0 (Week 0), Visit 9 (Week 52), and Visit 13 (Week 52) ] [ Designated as safety issue: Yes ]Major hypoglycemic events occurring from randomization at weeks 0, 52 and 104.
- Number and severity of adverse events [ Time Frame: Adverse Events will be assessed at Visit 0 (week 0), Visit 1 (Week 2), Visit 2 (Week 4), and every month thereafter. ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||September 2019|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Experimental: Imatinib Mesylate
400 mg imatinib given once daily basis.
Drug: Imatinib Mesylate
Placebo Comparator: Placebo
Placebo given once daily basis.
|Drug: Placebo (For imatinib mesylate)|
Eligible participants will be randomized to receive either imatinib mesylate or placebo daily.
All participants randomized into this study will be seen at a study site for a follow-up evaluation, 2 weeks and 4 weeks after randomization, and every month month thereafter for the first year. Participants will come in for a visit ever 6 months for the second year.
At the study visits, participants will undergo assessments of their insulin production, immunologic status, and overall health. Subjects will be followed until the conclusion of the study. The trial is expected to last approximately 2-4 years or until the required amount of information is gathered.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01781975
|United States, California|
|University of California-San Francisco|
|San Francisco, California, United States, 94143|
|United States, Colorado|
|Barbara Davis Center|
|Aurora, Colorado, United States, 80045|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, Iowa|
|University of Iowa|
|Iowa City, Iowa, United States, 52242|
|United States, Massachusetts|
|Joslin Diabetes Center|
|Boston, Massachusetts, United States, 02215|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|University of Texas Southwestern|
|Dallas, Texas, United States, 75390|
|Walter and Eliza Hall Institute of Medical Research|
|Melbourne, Victoria, Australia, 3050|
|Principal Investigator:||Stephen E Gitelman, MD||University of California, San Francisco|