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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Diabetes Mellitus, Type 1

Intervention: Aralast NP (Drug); Placebo (Drug)

Phase: Phase 2

Status: Withdrawn

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Gordon Weir, MD, Study Chair, Affiliation: Joslin Diabetes Center


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.

Clinical Details

Official title: Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC)

Secondary outcome:

MMTT-Stimulated Peak and 4-hour C-peptide AUC

MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time

Insulin Use in Units Per Kilogram Body Weight Per Day

Hypoglycemic Events Occurring from Randomization to End of Trial

Glycosylated Hemoglobin (HbA1c) Levels

Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies

Frequency and Severity of All Adverse Events (AEs)

Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance

Pharmacokinetic Parameters of 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.


Minimum age: 8 Years. Maximum age: 35 Years. Gender(s): Both.


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,


- 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

Locations and Contacts

University of California San Diego, La Jolla, California 92093, United States

Barbara Davis Center, Aurora, Colorado 80045, United States

Yale University, New Haven, Connecticut 06511, United States

Atlanta Diabetes Associates, Atlanta, Georgia 30309, United States

Emory University, Atlanta, Georgia 30322, United States

University of Iowa, Iowa City, Iowa 52242, United States

University of Maryland Medical Center, Baltimore, Maryland 21201, United States

Calvert Memorial Hospital, Prince Frederick, Maryland 20678, United States

Joslin Diabetes Center, Boston, Massachusetts 02215, United States

Massachusetts General Hospital, Boston, Massachusetts 02114, United States

University of Massachusetts Medical School, Worchester, Massachusetts 01655, United States

Columbia University, New York, New York 10027, United States

Nationwide Children's Hospital, Columbus, Ohio 43205, United States

The Children's Hospital of Philadelphia, Philadephia, Pennsylvania 19104, United States

Cetero Research San Antonio, San Antonio, Texas 78229, United States

Additional Information

National Institute of Allergy and Infectious Diseases (NIAID) website

Immune Tolerance Network website

Juvenile Diabetes Research Foundation (JDRF)

Starting date: October 2010
Last updated: December 30, 2014

Page last updated: August 23, 2015

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