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A Research Trial of Aralast in New Onset Diabetes (RETAIN) (RETAIN)

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ClinicalTrials.gov Identifier: NCT01183468
Recruitment Status : Terminated (Due to lack of mechanistic signal and competing industry studies)
First Posted : August 17, 2010
Results First Posted : January 16, 2015
Last Update Posted : June 13, 2018
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE August 16, 2010
First Posted Date  ICMJE August 17, 2010
Results First Submitted Date  ICMJE January 6, 2015
Results First Posted Date  ICMJE January 16, 2015
Last Update Posted Date June 13, 2018
Study Start Date  ICMJE October 2010
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2015)
C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 16, 2010)
Mixed-Meal Tolerance Test (MMTT)-stimulated 2-hour C-peptide Area under the curve (AUC) [ Time Frame: Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2010)
  • MMTT-stimulated peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ]
  • MMTT-stimulated 2-hour C-peptide AUC assessed longitudinally [ Time Frame: Weeks 0, 14, 26, 52, and 104 ]
  • Insulin use in units per kilogram body weight per day [ Time Frame: Weeks 52 and 104 ]
    Insulin use in units per kilogram body weight per day
  • Hypoglycemic events occurring from randomization [ Time Frame: Throughout the trial ]
  • Glycosylated Hemoglobin (HbA1C) Levels [ Time Frame: Weeks 52 and 104 ]
  • Emergence of anti-AAT antibodies [ Time Frame: Throughout the study ]
  • Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections) [ Time Frame: Throughout the study ]
  • Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance [ Time Frame: Throughout the trial ]
  • Pharmacokinetic parameters of Aralast NP [ Time Frame: Throughout the trial ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Research Trial of Aralast in New Onset Diabetes (RETAIN)
Official Title  ICMJE Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)
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.

Detailed Description

Researchers are interested in conducting this study to assess whether Aralast NP (AAT, Alpha-1 Antitrypsin ) will help slow the progression of T1DM.

Part I of this study has two parts:-1a and -1b:

Part 1a (Complete): An open-label, dose-escalation, PK, PD and safety study. Participants receive 12 intravenous (IV) infusions of Aralast NP. Infusions 1 through 6 are administered at 45 mg/kg/wk and infusions 7 through 12 are administered at 90 mg/kg/wk.

Part Ia consists of two groups:

  • Subjects aged 16 - 35 years at enrollment with new-onset T1DM
  • Subjects aged 8 -15 years at enrollment with new-onset T1DM.

Part 1b (study terminated prior to subject enrollment): An open-label, dose-escalation PK, PD and safety study in which participants receive 12 infusions of Aralast NP. Infusions 1 through 6 are administered at 90 mg/kg/wk and infusions 7 through 12 are administered at 180 mg/kg/wk. Part Ib consists of two groups:

  • Subjects aged 16 - 35 years at enrollment with new-onset T1DM
  • Subjects 8 - 15 years at enrollment with new-onset T1DM.

Participants in Part Ib do not roll over into Part II (Refer to NCT01183455).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Biological: Aralast NP 45 mg dose
    - 45 mg/kg/week
    Other Names:
    • Alpha 1-Antitrypsin
    • AAT
  • Biological: Aralast NP 90 mg dose
    - 90 mg/kg/week
    Other Names:
    • Alpha 1-Antitrypsin
    • AAT
  • Biological: Aralast NP 180 mg dose
    - 180 mg/kg/week
    Other Names:
    • Alpha-1 Antitrypsin
    • AAT
Study Arms  ICMJE
  • Experimental: Part 1a(Aralast NP)-Subjects Aged 16-35 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.
    Interventions:
    • Biological: Aralast NP 45 mg dose
    • Biological: Aralast NP 90 mg dose
  • Experimental: Part 1a (Aralast NP)-Subjects 8-15 Yrs
    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.
    Interventions:
    • Biological: Aralast NP 45 mg dose
    • Biological: Aralast NP 90 mg dose
  • Experimental: Part 1b (Aralast NP)--Subjects Aged 18-35 Yrs
    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.
    Interventions:
    • Biological: Aralast NP 90 mg dose
    • Biological: Aralast NP 180 mg dose
  • Experimental: Part 1b (Aralast NP)-Subjects 8-17 Yrs
    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.
    Interventions:
    • Biological: Aralast NP 90 mg dose
    • Biological: Aralast NP 180 mg dose
Publications * Ozeri E, Mizrahi M, Shahaf G, Lewis EC. α-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 14, 2015)
17
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2010)
16
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 35 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01183468
Other Study ID Numbers  ICMJE DAIT ITN041AI Part 1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Participant level data and additional relevant materials are available to the public in TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
Time Frame: IPD is now available in TrialShare.
Access Criteria: Open to the public.
URL: https://www.itntrialshare.org/project/Studies/ITN041AIPUBLIC/Study%20Data/begin.view?pageId=study.DATA_ANALYSIS
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Immune Tolerance Network (ITN)
  • Juvenile Diabetes Research Foundation
Investigators  ICMJE
Study Chair: Gordon Weir, MD Joslin Diabetes Center
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP