search
Back to results

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

Primary Purpose

Diabetes Mellitus, Type 1

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aralast NP
Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes Mellitus, Type 1 (new-onset), T1DM (new-onset), T1D (new-onset), Diabetes, Autoimmune, Alpha1-Proteinase Inhibitor, Alpha-1 Antitrypsin, AAT

Eligibility Criteria

8 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Diego
  • Barbara Davis Center
  • Yale University
  • Atlanta Diabetes Associates
  • Emory University
  • University of Iowa
  • University of Maryland Medical Center
  • Calvert Memorial Hospital
  • Massachusetts General Hospital
  • Joslin Diabetes Center
  • University of Massachusetts Medical School
  • Columbia University
  • Nationwide Children's Hospital
  • The Children's Hospital of Philadelphia
  • Cetero Research San Antonio

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aralast NP

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 16, 2010
Last Updated
December 30, 2014
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), Juvenile Diabetes Research Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT01183455
Brief Title
A Research Trial of Aralast NP in New Onset Diabetes (RETAIN) - Part II
Acronym
RETAIN
Official Title
Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor decision-lack of mechanistic signal and competing industry studies
Study Start Date
October 2010 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), Juvenile Diabetes Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Diabetes Mellitus, Type 1 (new-onset), T1DM (new-onset), T1D (new-onset), Diabetes, Autoimmune, Alpha1-Proteinase Inhibitor, Alpha-1 Antitrypsin, AAT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aralast NP
Arm Type
Experimental
Arm Description
Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo intravenously once a week for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Aralast NP
Other Intervention Name(s)
Alpha 1-Proteinase Inhibitor Human, Alpha,-antitrypsin, AAT
Intervention Description
Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for Aralast NP
Intervention Description
Participants will receive IV infusions of placebo once a week for 12 weeks.
Primary Outcome Measure Information:
Title
Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC)
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
MMTT-Stimulated Peak and 4-hour C-peptide AUC
Time Frame
Weeks 52 and 104
Title
MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time
Time Frame
Weeks 0, 14, 26, 52, and 104
Title
Insulin Use in Units Per Kilogram Body Weight Per Day
Time Frame
Weeks 52 and 104
Title
Hypoglycemic Events Occurring from Randomization to End of Trial
Time Frame
Throughout the Study
Title
Glycosylated Hemoglobin (HbA1c) Levels
Time Frame
Weeks 52 and 104
Title
Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies
Time Frame
Throughout the Study
Title
Frequency and Severity of All Adverse Events (AEs)
Time Frame
Throughout the study
Title
Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance
Time Frame
Throughout the study
Title
Pharmacokinetic Parameters of Aralast NP
Time Frame
Throughout the study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon Weir, MD
Organizational Affiliation
Joslin Diabetes Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Barbara Davis Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Atlanta Diabetes Associates
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Calvert Memorial Hospital
City
Prince Frederick
State/Province
Maryland
ZIP/Postal Code
20678
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Joslin Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worchester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10027
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadephia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Cetero Research San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.niaid.nih.gov
Description
National Institute of Allergy and Infectious Diseases (NIAID) website
URL
http://www.immunetolerance.org
Description
Immune Tolerance Network website
URL
http://jdrf.org/about-jdrf/
Description
Juvenile Diabetes Research Foundation (JDRF)

Learn more about this trial

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

We'll reach out to this number within 24 hrs