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Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus

Information source: University of California, San Francisco
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Diabetes Mellitus, Type I; Diabetes Mellitus, Insulin-Dependent, 1; Type 1 Diabetes Mellitus; Insulin-Dependent Diabetes Mellitus 1; IDDM

Intervention: Imatinib Mesylate (Drug); Placebo (For imatinib mesylate) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of California, San Francisco

Official(s) and/or principal investigator(s):
Stephen E Gitelman, MD, Principal Investigator, Affiliation: University of California, San Francisco

Overall contact:
Stephen E Gitelman, MD, Phone: 415-476-3748, Email: sgitelma@peds.ucsf.edu

Summary

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing 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.

Clinical Details

Official title: Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-Onset Type 1 Diabetes Mellitus

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Effect of treatment with imatinib versus placebo in individuals

Secondary outcome:

Mean area under the stimulated C-peptide curve (AUC) curve at 12 months

Mean area under the stimulated C-peptide curve (AUC) over 4 hours at 24 months

Change in HbA1c levels over time

Change in Insulin dose (units/kg) over time

Number of severe hypoglycemic events

Number and severity of adverse events

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Males and females age 12-45 years of age who meet the ADA standard T1DM criteria1.

Positive for at least one islet cell autoantibody. Initial enrollment will be for subjects ages 18-45, with the goal to lower the age down to 12 upon acceptable safety review and prospect of benefit for this initial older cohort.

- Diagnosis of T1DM within 100 days of Visit 0.

- Peak stimulated C-peptide level >0. 2 pmol/mL following an MMTT.

- Participants of childbearing age who are sexually active must agree to use an

effective form of birth control (e. g., barrier method, oral contraception, or surgery). For females, these contraceptive measures must be maintained throughout the study; for males these measures must be followed for a minimum of 3 months after discontinuation of imatinib therapy. Exclusion Criteria:

- Prior history of any significant cardiac disease such as congestive heart failure,

myocardial infarction, arrhythmia, or structural defects or suspicion thereof.

- Leukopenia (<3,000 leukocytes/μL), neutropenia (<1,500 neutrophils/μL), or

thrombocytopenia (<125,000 platelets/μL).

- Low Hemoglobin (baseline hemoglobin below lower limit of normal)

- Prior history of anaphylaxis, angioedema or serious cutaneous drug reactions

- Any sign of significant chronic active infection (e. g., hepatitis, tuberculosis, EBV,

CMV, or toxoplasmosis), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, PPD, or HBSAg). Significant acute infections must be resolved before treatment may commence, e. g., acute respiratory tract, urinary tract, or gastrointestinal tract infections.

- Anticipated ongoing use of diabetes medications other than insulin that affect

glucose homeostasis, such as metformin, sulfonylureas, thiazolidinediones, glucagon-like peptide 1 (GLP-1) mimetics, dipeptidyl peptidase IV (DPP-IV) inhibitors, or amylin.

- Prior or current treatment that is known to cause a significant, ongoing change in

the course of T1DM or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids.

- Evidence of liver dysfunction, with alanine aminotransferase (ALT) or aspartate

aminotransferase (AST) >2. 0 times the upper limit of normal persistent for 1 week or greater.

- Evidence of renal insufficiency as indicated by serum creatinine > 1. 2 times the

upper limit of normal and confirmed in a repeat test at least one week apart. Evidence of clinically significant metabolic bone disease (except adequately treated rickets).

- Females who are pregnant at the time of screening or unwilling to defer pregnancy

during the 24-month study period.

- Prior treatment with imatinib or related tyrosine kinase inhibitor.

- Unable to avoid medications that affect CYP3A4: either inducers that may decrease

imatinib levels, or inhibitors that may increase drug concentrations. (Refer to section 1. 5.1. 12 for a complete list of inducers and inhibitors.)

- Height standard deviation score ≥2 standard deviations below mean

- Any sign of QT prolongation on Visit -1 noted on ECG (> 450 ms in males and > 470 ms

in females)

- Known coagulation disorders or use of anticoagulants

- Current and anticipated on-going treatment with drugs that may increase or decrease

imatinib plasma concentrations (CYP3A4 family inhibitors or inducers) or drugs that may have their plasma concentration altered by imatinib (drugs metabolized by CYP3A4/5 and CYP2D6).

- Any condition that, in the investigator's opinion, may compromise study participation

or may confound the interpretation of the study results.

Locations and Contacts

Stephen E Gitelman, MD, Phone: 415-476-3748, Email: sgitelma@peds.ucsf.edu

University of California-San Francisco, San Francisco, California 94143, United States; Recruiting
Christine Torok, RN, Phone: 415-502-9089, Email: torokc@peds.ucsf.edu
Stephen E Gitelman, MD, Principal Investigator

Barbara Davis Center, Aurora, Colorado 80045, United States; Recruiting
Allison Schauwecker, Phone: 303-724-8615, Email: allison.shauwecker@ucdenver.edu
Peter Gottlieb, MD, Principal Investigator

Emory University, Atlanta, Georgia 30322, United States; Recruiting
Karen Lindsley, Phone: 404-727-1098, Email: klindsl@emory.edu
Eric Felner, MD, Principal Investigator

Indiana University, Indianapolis, Indiana 46202, United States; Recruiting
Jennifer K Terrell, Phone: 317-944-2584, Email: jkramey@iu.edu
Linda DiMeglio, MD, Principal Investigator

University of Iowa, Iowa City, Iowa 52242, United States; Recruiting
Joanne Cabbage, Phone: 319-356-4035, Email: joanne-cabbage@uiowa.edu
Eva Tsalikian, MD, Principal Investigator

Joslin Diabetes Center, Boston, Massachusetts 02215, United States; Recruiting
Brittany Resnick, BSN, RN, Phone: 617-309-4148, Email: Brittany.Resnick@joslin.harvard.edu
Jason Gaglia, MD, MMSc, Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Tammy Calvano, Phone: 267-426-3908, Email: calvanot@email.chop.edu
Steven M Willi, MD, Principal Investigator

University of Texas Southwestern, Dallas, Texas 75390, United States; Recruiting
Lourdes Pruneda, MSN, RN, Phone: 214-648-4717, Email: Maria.Pruneda@UTSouthwestern.edu
Phillip Raskin, MD CDE, Principal Investigator

Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia; Recruiting
Felicity Healy, Phone: 03-934-27672, Email: shelley.mesfin@mh.org.au
John Wentworth, MD, Principal Investigator

Additional Information

Starting date: January 2014
Last updated: March 20, 2015

Page last updated: August 23, 2015

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