TITLE: Eligibility (Part 4 of Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-onset Type 1 Diabetes Mellitus)
AUTHORS: Stephen.Gitelman , Jeffrey A. Bluestone

[DESCRIPTION]
<div class = "text-blocks"><div class = "text-block">This is Part 4 of "Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-Onset Type 1 Diabetes Mellitus".</div><div class = "text-block">This clinical study is supported by JDRF. The aim of the collection is to determine whether imatinib will slow the progression of the autoimmune destruction of ß cells and lead to the preservation of C-peptide secretion in T1DM and to assess Diabetes-related objectives and safety of Imatinib in new-onset type 1 diabetes mellitus".</div></div>

[STEPS]
?. [INCLUSION CRITERIA]
Patents must meet all of the following criteria:Males and females age 12–45 years of age who meet the ADA standard T1DM criteria.
?. [INCLUSION CRITERIA]
Positive for at least one islet cell autoantibody (glutamate decarboxylase; insulin, if obtained within 10 days of the onset of insulin therapy; ICA 512-antibody; and/or ICA or ZnT8).
?. [INCLUSION CRITERIA]
Diagnosis of T1DM within 100 days of Visit 0.
?. [INCLUSION CRITERIA]
Peak stimulated C-peptide level >0.2 pmol/mL following an MMTT.
?. [INCLUSION CRITERIA]
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]
Patients must not meet any of the following criteria:Prior history of any significant cardiac disease such as congestive heart failure, myocardial infarction, arrhythmia, or structural defects or suspicion thereof.
?. [EXCLUSION CRITERIA]
Leukopenia (
?. [EXCLUSION CRITERIA]
Low Hemoglobin (baseline hemoglobin below the lower limit of normal).
?. [EXCLUSION CRITERIA]
Prior history of anaphylaxis, angioedema or serious cutaneous drug reactions.
?. [EXCLUSION CRITERIA]
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/IGRA, or HBSAg). Significant acute infections must be resolved before treatment may commence, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections.
?. [EXCLUSION CRITERIA]
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.
?. [EXCLUSION CRITERIA]
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.
?. [EXCLUSION CRITERIA]
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.
?. [EXCLUSION CRITERIA]
Evidence of renal insufficiency as indicated by serum creatinine of >1.2 times the upper limit of normal confirmed in a repeat test at least 1 week apart.
?. [EXCLUSION CRITERIA]
Evidence of clinically significant metabolic bone disease (except adequately treated rickets).
?. [EXCLUSION CRITERIA]
Females who are pregnant at the time of screening, breastfeeding or unwilling to defer pregnancy during the 24-month study period. (Female participant must be at least 100 days postpartum before enrollment into study).
?. [EXCLUSION CRITERIA]
Prior treatment with imatinib or related tyrosine kinase inhibitor.
?. [EXCLUSION CRITERIA]
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.).
?. [EXCLUSION CRITERIA]
Height standard deviation score ≥2 standard deviations below mean (participants of growing-age potential).
?. [EXCLUSION CRITERIA]
Any sign of QT prolongation on Visit -1 ECG (> 450 ms in males and > 470 ms in females).
?. [EXCLUSION CRITERIA]
Known coagulation disorders or use of anticoagulants.
?. [EXCLUSION CRITERIA]
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).
?. [EXCLUSION CRITERIA]
Any condition that, in the investigator’s opinion, may compromise study participation or may confound the interpretation of the study results.