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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
67
University of California-San Francisco
San Francisco, California, United States
Barbara Davis Center
Aurora, Colorado, United States
Emory University
Atlanta, Georgia, United States
Indiana University
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
Joslin Diabetes Center
Boston, Massachusetts, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
University of Texas Southwestern
Dallas, Texas, United States
Walter and Eliza Hall Institute of Medical Research
Melbourne, Victoria, Australia
Area Under the Stimulated C-peptide Curve (AUC) Mean Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 1 Year Visit
The primary outcome of each participant is the area under the stimulated c-peptide curve (AUC) mean based on data collected at time 0 to 2 hours of a 4-hour mixed meal tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30, 60, 90, and 120 minutes. The term "AUC mean" comes from the mean value theorem in calculus. It is the value on the scale of the y-axis that is equal to the AUC divided by the range on the x-axis (in this case 120 minutes).
Time frame: Visit 9 (Week 52) at 0, 15, 30, 60, 90, 120 minutes post-dose
Area Under the Stimulated C-peptide Curve (AUC) Mean Over 4 Hours at 24 Months
Area under the MMTT-stimulated peak, 4 hour C-peptide AUC mean at week 104. The units are reported as nano-moles/Liter because this is AUC mean (the AUC is divided by the time internal so that the units return to the c-peptide units of measure).
Time frame: Visit 13 (Week 104)
Change in HbA1c Levels Over Time
Change in HbA1c levels from Week 52 to Week 104
Time frame: Visit 9 (Week 52) and Visit 13 (Week 104)
Change in Insulin Dose (Units/kg) Over Time
Assess insulin use in units per kilogram body weight per day at weeks 52 and 104.
Time frame: Visit 9 (Week 52) and Visit 13 (Week 104)
Number of Severe Hypoglycemic Events
Major hypoglycemic events occurring from randomization at weeks 0, 52 and 104.
Time frame: Visit 0 (Week 0), Visit 9 (Week 52), and Visit 13 (Week 104)
Number of Adverse Events
Number of adverse events that were reported throughout the study.
Time frame: Adverse Events will be assessed at Visit 0 (week 0), Visit 1 (Week 2), Visit 2 (Week 4), and every month thereafter.
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