Study Stopped
Due to lack of mechanistic signal and competing industry studies
A Research Trial of Aralast in New Onset Diabetes (RETAIN)
RETAIN
Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)
1 other identifier
interventional
17
1 country
15
Brief Summary
The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's normal ability to fight infection and respond to injuries) that affects the cells thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). All subjects enrolled in this study have new-onset T1DM (diagnosis of T1DM within 100 days of Visit 0; T1DM diagnosis fulfilling American Diabetes Association standard T1DM criteria). The focus of Part I of this trial (NCT01183468) is pharmacokinetics (PK), pharmacodynamics (PD) and safety. Upon completion of Part I, including a satisfactory safety review, enrollment in Part II (NCT01183455, Phase II Clinical Trial) will begin.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2010
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 16, 2010
CompletedFirst Posted
Study publicly available on registry
August 17, 2010
CompletedStudy Start
First participant enrolled
October 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2013
CompletedResults Posted
Study results publicly available
January 16, 2015
CompletedJune 13, 2018
May 1, 2018
2.8 years
August 16, 2010
January 6, 2015
May 14, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52
No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks.
Week 52
Study Arms (4)
Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs
EXPERIMENTALSubjects 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.
Part 1a (Aralast NP)-Subjects 8-15 Yrs
EXPERIMENTALSubjects 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.
Part 1b (Aralast NP)--Subjects Aged 18-35 Yrs
EXPERIMENTALAralast 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.
Part 1b (Aralast NP)-Subjects 8-17 Yrs
EXPERIMENTALAralast 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.
Interventions
\- 45 mg/kg/week
\- 90 mg/kg/week
\- 180 mg/kg/week
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
RADY Children's Hospital (University of California, San Diego)
San Diego, California, 92093, United States
Barbara Davis Center (University of Colorado)
Aurora, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06520, United States
Atlanta Diabetes Associates
Atlanta, Georgia, 30309, United States
Children's Hospital of Atlanta (Emory University)
Atlanta, Georgia, 30322, United States
University of Iowa Children's Hospital
Iowa City, Iowa, 52242, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Joslin Diabetes Center
Boston, Massachusetts, 02215, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Naomi Berrie Diabetes Center (Columbia University)
New York, New York, 10032, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Pacific Northwest Research Institute-University of Washington
Seattle, Washington, 98122, United States
Related Publications (1)
Ozeri E, Mizrahi M, Shahaf G, Lewis EC. alpha-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol. 2012 Jul 1;189(1):146-53. doi: 10.4049/jimmunol.1101340. Epub 2012 May 25.
PMID: 22634621DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This (Part 1) was the drug dosing portion of the study; however, due to lack of a mechanistic signal and competing industry studies, the study was terminated and the trial portion (Part II, NCT01183455) was withdrawn.
Results Point of Contact
- Title
- Director, Clinical Research Operations Program
- Organization
- DAIT/NIAID
Study Officials
- STUDY CHAIR
Gordon Weir, MD
Joslin Diabetes Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 16, 2010
First Posted
August 17, 2010
Study Start
October 1, 2010
Primary Completion
July 1, 2013
Study Completion
July 1, 2013
Last Updated
June 13, 2018
Results First Posted
January 16, 2015
Record last verified: 2018-05
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- IPD is now available in TrialShare.
- Access Criteria
- Open to the public.
Participant level data and additional relevant materials are available to the public in TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.