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

Condition(s) targeted: Diabetes Mellitus, Type 1

Intervention: Alpha 1-Antitrypsin (AAT, Aralast NP) (Drug); Placebo (Drug)

Phase: Phase 2

Status: Not yet recruiting

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

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.

Official title: Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus - 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 longitudinally

Insulin use in units per kilogram body weight per day

Hypoglycemic events occurring from randomization

Glycosylated hemoglobin (HbA1C) levels

Emergence of anti-AAT antibodies

Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections)

Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance

Pharmacokinetic parameters of Aralast NP

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.

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

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.

University of California San Diego, La Jolla, California 92093, United States; Not yet recruiting
Michael Gottschalk, MD, Principal Investigator

Barbara Davis Center, Aurora, Colorado 80045, United States; Not yet recruiting
Peter Gottlieb, MD, Principal Investigator

Yale University, New Haven, Connecticut 06511, United States; Not yet recruiting
Kevin Herold, MD, Principal Investigator

Emory University, Atlanta, Georgia 30322, United States; Not yet recruiting
Mark Rigby, MD, PhD, Principal Investigator
Eric Felner, MD, Principal Investigator

Atlanta Diabetes Associates, Atlanta, Georgia 30309, United States; Not yet recruiting
Bruce Bode, MD, Principal Investigator

University of Iowa, Iowa City, Iowa 52242, United States; Not yet recruiting
Eva Tsalikian, MD, Principal Investigator

University of Maryland Medical Center, Baltimore, Maryland 21201, United States; Not yet recruiting
Debra Counts, MD, Principal Investigator

Calvert Memorial Hospital, Prince Frederick, Maryland 20678, United States; Not yet recruiting
June Moore, MD, Principal Investigator

Joslin Diabetes Center, Boston, Massachusetts 02215, United States; Not yet recruiting
Gordon Weir, MD, Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Not yet recruiting
Nicole A Sherry, MD, Principal Investigator

University of Massachusetts Medical School, Worchester, Massachusetts 01655, United States; Not yet recruiting
Mary Lee, MD, Principal Investigator

Columbia University, New York, New York 100027, United States; Not yet recruiting
Robin Goland, MD, Principal Investigator

Nationwide Children's Hospital, Columbus, Ohio 43205, United States; Not yet recruiting
Timothy Hoffman, MD, Principal Investigator

The Children's Hospital of Philadelphia, Philadephia, Pennsylvania 19104, United States; Not yet recruiting
Steven M Willi, MD, Principal Investigator

Cetero Research San Antonio, San Antonio, Texas 78229, United States; Not yet recruiting
Jolene Berg, MD, Principal Investigator

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Click here for the National Institute of Allergy and Infectious Diseases website

Starting date: October 2010
Last updated: August 16, 2010