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A Research Trial of Aralast NP in New Onset Diabetes (RETAIN) - Part II (RETAIN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01183455
Recruitment Status : Withdrawn (Sponsor decision-lack of mechanistic signal and competing industry studies)
First Posted : August 17, 2010
Last Update Posted : December 31, 2014
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
Last Update Posted Date December 31, 2014
Study Start Date  ICMJE October 2010
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2014)
Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) [ Time Frame: Week 52 ]
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
 (submitted: October 20, 2014)
  • MMTT-Stimulated Peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ]
  • MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time [ 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 ]
  • Hypoglycemic Events Occurring from Randomization to End of Trial [ Time Frame: Throughout the Study ]
  • Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Weeks 52 and 104 ]
  • Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies [ Time Frame: Throughout the Study ]
  • Frequency and Severity of All Adverse Events (AEs) [ Time Frame: Throughout the study ]
  • Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance [ Time Frame: Throughout the study ]
  • Pharmacokinetic Parameters of Aralast NP [ Time Frame: Throughout the study ]
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 ]
  • 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 trial ]
  • 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 NP in New Onset Diabetes (RETAIN) - Part II
Official Title  ICMJE Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Drug: Aralast NP
    Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.
    Other Names:
    • Alpha 1-Proteinase Inhibitor Human
    • Alpha,-antitrypsin
    • AAT
  • Drug: Placebo
    Participants will receive IV infusions of placebo once a week for 12 weeks.
    Other Name: Placebo for Aralast NP
Study Arms  ICMJE
  • Experimental: Aralast NP
    Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.
    Intervention: Drug: Aralast NP
  • Placebo Comparator: Placebo
    Participants will receive placebo intravenously once a week for 12 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 20, 2014)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2010)
66
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
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 NCT01183455
Other Study ID Numbers  ICMJE DAIT ITN041AI Part II
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Associate Director, Clinical Research and Operations Program, DAIT, NIAID, NIH
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
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 December 2014

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