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

This study has been withdrawn prior to enrollment.
(Sponsor decision-lack of mechanistic signal and competing industry studies)
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01183455
First received: August 16, 2010
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

Aralast NP, 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 (T1D, T1DM). 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) is 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 Intervention Phase
Diabetes Mellitus, Type 1
Drug: Aralast NP
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 - Part II

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MMTT-Stimulated Peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time [ Time Frame: Weeks 0, 14, 26, 52, and 104 ] [ Designated as safety issue: No ]
  • Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • Hypoglycemic Events Occurring from Randomization to End of Trial [ Time Frame: Throughout the Study ] [ Designated as safety issue: Yes ]
  • Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies [ Time Frame: Throughout the Study ] [ Designated as safety issue: Yes ]
  • Frequency and Severity of All Adverse Events (AEs) [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic Parameters of Aralast NP [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: October 2010
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   8 Years to 35 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Investigators
Study Chair: Gordon Weir, MD Joslin Diabetes Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01183455     History of Changes
Other Study ID Numbers: DAIT ITN041AI PartII
Study First Received: August 16, 2010
Last Updated: October 20, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 23, 2014