A Research Trial of Aralast NP in New Onset Diabetes (RETAIN) - Part II
- Registration Number
- NCT01183455
- Brief Summary
Aralast NP (alpha-1 antitrypsin, AAT), an alpha-1 proteinase inhibitor (human), was the drug to be tested in this clinical trial. Aralast NP is an anti-inflammatory drug that affects the cells that are thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). This study, known as RETAIN, was planned as a two-part trial to investigate the effect of Aralast NP on preserving beta cell function and to determine if the intervention would slow the progression of type 1 diabetes.
Part I of this trial (NCT 01183468) was an open-label, safety and dose level study consisting of two groups. After completion of Part I, including a satisfactory safety review, enrollment in Part II was to begin. Part II was designed as a two-arm, double-blind, placebo-controlled clinical trial, and participants were to be randomly assigned to either the Aralast NP treatment or placebo group.
- Detailed Description
T1D is an autoimmune disease. This means that your immune system (the part of your body that helps fight infections) mistakenly attacks the cells that produce insulin (beta cells in the pancreas). As beta cells are destroyed by your immune cells, your ability to produce insulin is decreased. Insulin helps keep blood glucose levels normal.
Individuals with T1D who have the ability to produce some of their own insulin (even though they still need to take insulin) may be able to achieve better glucose control than people who produce no insulin at all. Better glucose control has been shown to reduce the long-term complications of diabetes. Previous research has shown that giving medicines to affect the immune system soon after type 1 diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.
In mouse models of disease, alpha-1 proteinase inhibitors have been shown to reverse new-onset diabetes and induce a state of self-tolerance. The RETAIN clinical trial was intended to investigate the effect of Aralast NP on preserving beta cell function and slowing the progression of T1D.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Diagnosed with type 1 diabetes (T1D) within the past 100 days
- 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 greater than (>) 0.2 pmol/mL following a mixed meal tolerance test (MMTT)
- Severe active disease (hepatitis, cardiac or pulmonary disease, hypertension, immunodeficiency)
- History of any bleeding or clotting factor deficiencies, or stroke
- History of vascular disease or significant vascular abnormalities
- Positive serology exposure to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or toxoplasmosis
- Clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV), 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 T1D or immunologic status
- Prior treatment with alpha1-antitrypsin (AAT) or hypersensitivity to AAT 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
- Immunoglobulin A (IgA) 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aralast NP Aralast NP Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks. Placebo Placebo Participants will receive placebo intravenously once a week for 12 weeks.
- Primary Outcome Measures
Name Time Method Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) Week 52
- Secondary Outcome Measures
Name Time Method Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies Throughout the Study MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time Weeks 0, 14, 26, 52, and 104 Hypoglycemic Events Occurring from Randomization to End of Trial Throughout the Study MMTT-Stimulated Peak and 4-hour C-peptide AUC Weeks 52 and 104 Insulin Use in Units Per Kilogram Body Weight Per Day Weeks 52 and 104 Frequency and Severity of All Adverse Events (AEs) Throughout the study Pharmacokinetic Parameters of Aralast NP Throughout the study Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance Throughout the study Glycosylated Hemoglobin (HbA1c) Levels Weeks 52 and 104
Trial Locations
- Locations (15)
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Massachusetts Medical School
🇺🇸Worchester, Massachusetts, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Barbara Davis Center
🇺🇸Aurora, Colorado, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Atlanta Diabetes Associates
🇺🇸Atlanta, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Calvert Memorial Hospital
🇺🇸Prince Frederick, Maryland, United States
Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
The Children's Hospital of Philadelphia
🇺🇸Philadephia, Pennsylvania, United States
Columbia University
🇺🇸New York, New York, United States
Cetero Research San Antonio
🇺🇸San Antonio, Texas, United States