Trial record 4 of 1365 for:    "type 1 diabetes" OR "Diabetes Mellitus, Type 1"

Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of California, San Francisco
Sponsor:
Collaborator:
JDRF
Information provided by (Responsible Party):
Stephen E. Gitelman, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01781975
First received: January 17, 2013
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type I
Diabetes Mellitus, Insulin-Dependent, 1
Type 1 Diabetes Mellitus
Insulin-Dependent Diabetes Mellitus 1
IDDM
Drug: Imatinib Mesylate
Drug: Placebo (For imatinib mesylate)
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 66
Study Start Date: January 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib Mesylate
400 mg imatinib given once daily basis.
Drug: Imatinib Mesylate
Other Names:
  • GLEEVEC
  • Glivec
Placebo Comparator: Placebo
Placebo given once daily basis.
Drug: Placebo (For imatinib mesylate)

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01781975

Contacts
Contact: Stephen E Gitelman, MD 415-476-3748 sgitelma@peds.ucsf.edu
Contact: Jeffrey A Bluestone, Ph.D. 415-514-1683 jbluest@diabetes.ucsf.edu

Locations
United States, California
University of California-San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Chrinstine Torok, RN    415-502-9089    torokc@peds.ucsf.edu   
Principal Investigator: Stephen E Gitelman, MD         
United States, Colorado
Barbara Davis Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Jennifer Smith    303-724-8272    jennifer.e.smith@ucdenver.edu   
Principal Investigator: Peter Gottlieb, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Nicholas Raviele    404-727-3189    nicholas.raviele@emory.edu   
Principal Investigator: Eric Felner, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Jennifer K Terrell    317-944-2584    jkramey@iu.edu   
Principal Investigator: Linda DiMeglio, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Joanne Cabbage    319-356-4035    joanne-cabbage@uiowa.edu   
Principal Investigator: Eva Tsalikian, MD         
United States, Massachusetts
Joslin Diabetes Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Brittany Resnick, BSN, RN    617-309-4148    Brittany.Resnick@joslin.harvard.edu   
Principal Investigator: Jason Gaglia, MD, MMSc         
United States, Nebraska
Creighton Diabetes Center Recruiting
Omaha, Nebraska, United States, 68131
Contact: Chris Smith    402-280-4319    christosmith@live.com   
Principal Investigator: Marc Rendell, MA         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Charles Isaacs    267-426-9218    isaacsc@email.chop.edu   
Principal Investigator: Steven M Willi, MD         
United States, Texas
University of Texas Southwestern Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Lourdes Pruneda, MSN, RN    214-648-4717    Maria.Pruneda@UTSouthwestern.edu   
Principal Investigator: Phillip Raskin, M.D. FACP, FACE, CDE         
Sponsors and Collaborators
University of California, San Francisco
JDRF
Investigators
Principal Investigator: Stephen E Gitelman, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Stephen E. Gitelman, Director, Pediatric Diabetes Program, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01781975     History of Changes
Other Study ID Numbers: 17-2013-6
Study First Received: January 17, 2013
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014