A Research Trial of Aralast in New Onset Diabetes (RETAIN) (RETAIN)
Diabetes Mellitus, Type 1
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes Mellitus, Type 1 (new-onset), Diabetes Mellitus, Insulin-Dependent (new-onset), new-onset T1DM, new-onset T1D, Diabetes Mellitus, Juvenile-Onset, Diabetes, Autoimmune, Aralast NP, Alpha-1 Antitrypsin, AAT
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with T1DM within the past 100 days (of enrollment)
- Positive for at least one diabetes-related autoantibody (Anti-GAD; Anti-insulin, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody and/or ICA, or ZnT8.)
- Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed meal tolerance test (MMTT)
Exclusion Criteria:
- Severe active disease (chronic active hepatitis; cardiac, pulmonary disease, hepatic, renal or immunodeficiency)
- History of any bleeding or clotting factor deficiencies, or stroke
- History of vascular disease or significant vascular abnormalities
- Positive serology of exposure to (hepatitis B virus) HBV, HCV (hepatitis C virus), HIV (human immunodeficiency virus) or toxoplasmosis
- Clinically active infection with EBV (Epstein-Barr virus), CMV (cytomegalovirus), or tuberculosis(TB)
- Prior or current use of oral, inhaled or intranasal glucocorticoids, or any medication known to cause a significant, ongoing change in the course of T1DM or immunologic status
- Prior treatment with Alpha 1-Antitrypsin (Aralast NP, AAT) or hypersensitivity to alpha 1-antitrypsin or human plasma-derived products
- Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin
- Current use of any medication known to influence glucose tolerance (e.g., beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, lithium, niacin)
- Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation
- IgA (immunoglobulin A) deficiency
- Uncontrolled hypertension
- Current life-threatening malignancy
- Any condition that in the investigator's opinion may compromise study participation or may confound the interpretation of the study results.
Sites / Locations
- RADY Children's Hospital (University of California, San Diego)
- Barbara Davis Center (University of Colorado)
- Yale University
- Atlanta Diabetes Associates
- Children's Hospital of Atlanta (Emory University)
- University of Iowa Children's Hospital
- University of Maryland Medical Center
- Massachusetts General Hospital
- Joslin Diabetes Center
- University of Massachusetts Memorial Medical Center
- Children's Mercy Hospital
- Naomi Berrie Diabetes Center (Columbia University)
- Nationwide Children's Hospital
- Children's Hospital of Philadelphia
- Pacific Northwest Research Institute-University of Washington
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs
Part 1a (Aralast NP)-Subjects 8-15 Yrs
Part 1b (Aralast NP)--Subjects Aged 18-35 Yrs
Part 1b (Aralast NP)-Subjects 8-17 Yrs
Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.