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

NCT ID: NCT01183455

Last Updated: 2014-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2014-08-31

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus, Type 1

Keywords

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Diabetes Mellitus, Type 1 (new-onset) T1DM (new-onset) T1D (new-onset) Diabetes, Autoimmune Alpha1-Proteinase Inhibitor Alpha-1 Antitrypsin AAT

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Aralast NP

Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.

Group Type EXPERIMENTAL

Aralast NP

Intervention Type DRUG

Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.

Placebo

Participants will receive placebo intravenously once a week for 12 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive IV infusions of placebo once a week for 12 weeks.

Interventions

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Aralast NP

Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.

Intervention Type DRUG

Placebo

Participants will receive IV infusions of placebo once a week for 12 weeks.

Intervention Type DRUG

Other Intervention Names

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Alpha 1-Proteinase Inhibitor Human Alpha,-antitrypsin AAT Placebo for Aralast NP

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Immune Tolerance Network (ITN)

NETWORK

Sponsor Role collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gordon Weir, MD

Role: STUDY_CHAIR

Joslin Diabetes Center

Locations

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University of California San Diego

La Jolla, California, United States

Site Status

Barbara Davis Center

Aurora, Colorado, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Calvert Memorial Hospital

Prince Frederick, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Joslin Diabetes Center

Boston, Massachusetts, United States

Site Status

University of Massachusetts Medical School

Worchester, Massachusetts, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

The Children's Hospital of Philadelphia

Philadephia, Pennsylvania, United States

Site Status

Cetero Research San Antonio

San Antonio, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.niaid.nih.gov

National Institute of Allergy and Infectious Diseases (NIAID) website

http://www.immunetolerance.org

Immune Tolerance Network website

http://jdrf.org/about-jdrf/

Juvenile Diabetes Research Foundation (JDRF)

Other Identifiers

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DAIT ITN041AI Part II

Identifier Type: -

Identifier Source: org_study_id