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

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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Recruitment Status : Withdrawn (Sponsor decision-lack of mechanistic signal and competing industry studies)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)

Study Description
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Aralast NP Drug: Placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II
Study Start Date : October 2010
Actual Primary Completion Date : August 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Aralast NP
Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.
 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
Placebo Comparator: Placebo
Participants will receive placebo intravenously once a week for 12 weeks.
 Drug: Placebo
Participants will receive IV infusions of placebo once a week for 12 weeks.
Other Name: Placebo for Aralast NP


Outcome Measures
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Primary Outcome Measures :
  1. Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) [ Time Frame: Week 52 ]

Secondary Outcome Measures :
  1. MMTT-Stimulated Peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ]
  2. MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time [ Time Frame: Weeks 0, 14, 26, 52, and 104 ]
  3. Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: Weeks 52 and 104 ]
  4. Hypoglycemic Events Occurring from Randomization to End of Trial [ Time Frame: Throughout the Study ]
  5. Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Weeks 52 and 104 ]
  6. Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies [ Time Frame: Throughout the Study ]
  7. Frequency and Severity of All Adverse Events (AEs) [ Time Frame: Throughout the study ]
  8. Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance [ Time Frame: Throughout the study ]
  9. Pharmacokinetic Parameters of Aralast NP [ Time Frame: Throughout the study ]

Eligibility Criteria
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Ages Eligible for Study:   8 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01183455


Locations
United States, California
University of California San Diego
La Jolla, California, United States, 92093
United States, Colorado
Barbara Davis Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06511
United States, Georgia
Atlanta Diabetes Associates
Atlanta, Georgia, United States, 30309
Emory University
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Calvert Memorial Hospital
Prince Frederick, Maryland, United States, 20678
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
University of Massachusetts Medical School
Worchester, Massachusetts, United States, 01655
United States, New York
Columbia University
New York, New York, United States, 10027
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadephia, Pennsylvania, United States, 19104
United States, Texas
Cetero Research San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Investigators
Study Chair: Gordon Weir, MD Joslin Diabetes Center
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
National Institute of Allergy and Infectious Diseases (NIAID) website  This link exits the ClinicalTrials.gov site
Immune Tolerance Network website  This link exits the ClinicalTrials.gov site
Juvenile Diabetes Research Foundation (JDRF)  This link exits the ClinicalTrials.gov site

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01183455     History of Changes
Other Study ID Numbers: DAIT ITN041AI Part II
First Posted: August 17, 2010    Key Record Dates
Last Update Posted: December 31, 2014
Last Verified: December 2014

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Diabetes Mellitus, Type 1 (new-onset)
T1DM (new-onset)
T1D (new-onset)
Diabetes, Autoimmune
 Alpha1-Proteinase Inhibitor
Alpha-1 Antitrypsin
AAT

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
 Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action