A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part II - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	Immune Tolerance Network (ITN) Juvenile Diabetes Research Foundation
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01183455

Purpose

The drug Alpha-1 Antitrypsin (AAT, Aralast NP), which is being tested in this clinical trial, is an anti-inflammatory drug that affects the cells that are thought to be involved in the development of type 1 diabetes. This trial, known as RETAIN, is a clinical trial is a two-part trial investigating the effect of intravenous Alpha-1 Antitrypsin(AAT, Aralast NP) on preserving beta cell function and to determine if AAT will help slow the progression of type 1 diabetes.

Part I of this trial (NCT#) is an open-label, safety and dose level study consisting of two groups. After Part I is completed, including a satisfactory safety review, enrollment in Part II will begin. Part II is a two-arm, double-blind, placebo-controlled clinical trial, and participants will be randomly assigned to either the treatment or placebo group.

Condition	Intervention	Phase
Diabetes Mellitus, Type 1	Drug: Alpha 1-Antitrypsin (AAT, Aralast NP) Drug: Placebo	Phase II

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:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Medicines Diabetes Type 1

U.S. FDA Resources

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 longitudinally [ 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 [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
Glycosylated hemoglobin (HbA1C) levels [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
Emergence of anti-AAT antibodies [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections) [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
Pharmacokinetic parameters of Aralast NP [ Time Frame: Throughout the trial ] [ Designated as safety issue: No ]

Estimated Enrollment:	66
Study Start Date:	October 2010
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Aralast NP	Drug: Alpha 1-Antitrypsin (AAT, Aralast NP) Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks. Other Names: AAT Aralast NP
Placebo Comparator: Placebo	Drug: Placebo Participants will receive IV infusions of an inactive placebo once a week for 12 weeks.

Detailed Description:

Type 1 diabetes mellitus 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.

People with type 1 diabetes 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 Antitrypsin (AAT, Aralast NP) has been shown to reverse new-onset diabetes and induce a state of self-tolerance. The RETAIN clinical trial is investigating the effect of intravenous Alpha-1 antitrypsin(AAT, Aralast NP) on preserving beta cell function and whether AAT will help slow the progression of type 1 diabetes.

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 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 > 0.2 pmol/mL following a mixed meal tolerance test (MMTT)

Exclusion Criteria:

Serve 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 HBV, HCV, HIV or toxoplasmosis
Clinically active infection with EBV, CMV, or tuberculosis
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 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.
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183455

Locations

United States, California
University of California San Diego	Not yet recruiting
La Jolla, California, United States, 92093
Principal Investigator: Michael Gottschalk, MD
United States, Colorado
Barbara Davis Center	Not yet recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Peter Gottlieb, MD
United States, Connecticut
Yale University	Not yet recruiting
New Haven, Connecticut, United States, 06511
Principal Investigator: Kevin Herold, MD
United States, Georgia
Emory University	Not yet recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Mark Rigby, MD, PhD
Principal Investigator: Eric Felner, MD
Atlanta Diabetes Associates	Not yet recruiting
Atlanta, Georgia, United States, 30309
Principal Investigator: Bruce Bode, MD
United States, Iowa
University of Iowa	Not yet recruiting
Iowa City, Iowa, United States, 52242
Principal Investigator: Eva Tsalikian, MD
United States, Maryland
University of Maryland Medical Center	Not yet recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Debra Counts, MD
Calvert Memorial Hospital	Not yet recruiting
Prince Frederick, Maryland, United States, 20678
Principal Investigator: June Moore, MD
United States, Massachusetts
Joslin Diabetes Center	Not yet recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Gordon Weir, MD
Massachusetts General Hospital	Not yet recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Nicole A Sherry, MD
University of Massachusetts Medical School	Not yet recruiting
Worchester, Massachusetts, United States, 01655
Principal Investigator: Mary Lee, MD
United States, New York
Columbia University	Not yet recruiting
New York, New York, United States, 100027
Principal Investigator: Robin Goland, MD
United States, Ohio
Nationwide Children's Hospital	Not yet recruiting
Columbus, Ohio, United States, 43205
Principal Investigator: Timothy Hoffman, MD
United States, Pennsylvania
The Children's Hospital of Philadelphia	Not yet recruiting
Philadephia, Pennsylvania, United States, 19104
Principal Investigator: Steven M Willi, MD
United States, Texas
Cetero Research San Antonio	Not yet recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Jolene Berg, MD

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

Additional Information:

Click here for Immune Tolerance Network website This link exits the ClinicalTrials.gov site

Click here for the National Institute of Allergy and Infectious Diseases website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Associate Director, Clinical Research and Operations Program, DAIT, NIAID, NIH
ClinicalTrials.gov Identifier:	NCT01183455 History of Changes
Other Study ID Numbers:	DAIT ITN041AIPartII
Study First Received:	August 16, 2010
Last Updated:	August 16, 2010
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
Diabetes Mellitus, Insulin-Dependent
Diabetes Mellitus, Juvenile-Onset

Diabetes, Autoimmune
Aralast NP
Alpha-1 Antitrypsin

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
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012