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

Diabetes Mellitus, Type 1 Clinical Trial

— RETAIN  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01183455
• Other study ID #: DAIT ITN041AI Part II
• Status: Withdrawn
• Phase: Phase 2
• First received: August 16, 2010
• Last updated: December 30, 2014
• Start date: October 2010
• Est. completion date: August 2014

Study information

• Verified date: December 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 35 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

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

Locations

Country	Name	City	State
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Barbara Davis Center	Aurora	Colorado
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Iowa	Iowa City	Iowa
United States	University of California San Diego	La Jolla	California
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	The Children's Hospital of Philadelphia	Philadephia	Pennsylvania
United States	Calvert Memorial Hospital	Prince Frederick	Maryland
United States	Cetero Research San Antonio	San Antonio	Texas
United States	University of Massachusetts Medical School	Worchester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN), Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC)		Week 52	No
Secondary	MMTT-Stimulated Peak and 4-hour C-peptide AUC		Weeks 52 and 104	No
Secondary	MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time		Weeks 0, 14, 26, 52, and 104	No
Secondary	Insulin Use in Units Per Kilogram Body Weight Per Day		Weeks 52 and 104	No
Secondary	Hypoglycemic Events Occurring from Randomization to End of Trial		Throughout the Study	Yes
Secondary	Glycosylated Hemoglobin (HbA1c) Levels		Weeks 52 and 104	No
Secondary	Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies		Throughout the Study	Yes
Secondary	Frequency and Severity of All Adverse Events (AEs)		Throughout the study	Yes
Secondary	Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance		Throughout the study	Yes
Secondary	Pharmacokinetic Parameters of Aralast NP		Throughout the study	No

External Links

•   Immune Tolerance Network website
•   Juvenile Diabetes Research Foundation (JDRF)
•   National Institute of Allergy and Infectious Diseases (NIAID) website