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

Primary Purpose

Diabetes Mellitus, Type 1

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Aralast NP 45 mg dose
Aralast NP 90 mg dose
Aralast NP 180 mg dose
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), Diabetes Mellitus, Insulin-Dependent (new-onset), new-onset T1DM, new-onset T1D, Diabetes Mellitus, Juvenile-Onset, Diabetes, Autoimmune, Aralast NP, Alpha-1 Antitrypsin, AAT

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosed with T1DM within the past 100 days (of enrollment)
  • 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:

  • Severe active disease (chronic active hepatitis; cardiac, pulmonary disease, hepatic, renal or immunodeficiency)
  • History of any bleeding or clotting factor deficiencies, or stroke
  • History of vascular disease or significant vascular abnormalities
  • Positive serology of exposure to (hepatitis B virus) HBV, HCV (hepatitis C virus), HIV (human immunodeficiency virus) or toxoplasmosis
  • Clinically active infection with EBV (Epstein-Barr virus), CMV (cytomegalovirus), 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 T1DM or immunologic status
  • Prior treatment with Alpha 1-Antitrypsin (Aralast NP, AAT) or hypersensitivity to alpha 1-antitrypsin 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 (immunoglobulin A) 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

  • RADY Children's Hospital (University of California, San Diego)
  • Barbara Davis Center (University of Colorado)
  • Yale University
  • Atlanta Diabetes Associates
  • Children's Hospital of Atlanta (Emory University)
  • University of Iowa Children's Hospital
  • University of Maryland Medical Center
  • Massachusetts General Hospital
  • Joslin Diabetes Center
  • University of Massachusetts Memorial Medical Center
  • Children's Mercy Hospital
  • Naomi Berrie Diabetes Center (Columbia University)
  • Nationwide Children's Hospital
  • Children's Hospital of Philadelphia
  • Pacific Northwest Research Institute-University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs

Part 1a (Aralast NP)-Subjects 8-15 Yrs

Part 1b (Aralast NP)--Subjects Aged 18-35 Yrs

Part 1b (Aralast NP)-Subjects 8-17 Yrs

Arm Description

Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.

Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.

Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.

Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.

Outcomes

Primary Outcome Measures

C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52
No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks.

Secondary Outcome Measures

Full Information

First Posted
August 16, 2010
Last Updated
May 14, 2018
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), Juvenile Diabetes Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01183468
Brief Title
A Research Trial of Aralast in New Onset Diabetes (RETAIN)
Acronym
RETAIN
Official Title
Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Terminated
Why Stopped
Due to lack of mechanistic signal and competing industry studies
Study Start Date
October 2010 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (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
The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's normal ability to fight infection and respond to injuries) that affects the cells thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). All subjects enrolled in this study have new-onset T1DM (diagnosis of T1DM within 100 days of Visit 0; T1DM diagnosis fulfilling American Diabetes Association standard T1DM criteria). The focus of Part I of this trial (NCT01183468) is pharmacokinetics (PK), pharmacodynamics (PD) and safety. Upon completion of Part I, including a satisfactory safety review, enrollment in Part II (NCT01183455, Phase II Clinical Trial) will begin.
Detailed Description
Researchers are interested in conducting this study to assess whether Aralast NP (AAT, Alpha-1 Antitrypsin ) will help slow the progression of T1DM. Part I of this study has two parts:-1a and -1b: Part 1a (Complete): An open-label, dose-escalation, PK, PD and safety study. Participants receive 12 intravenous (IV) infusions of Aralast NP. Infusions 1 through 6 are administered at 45 mg/kg/wk and infusions 7 through 12 are administered at 90 mg/kg/wk. Part Ia consists of two groups: Subjects aged 16 - 35 years at enrollment with new-onset T1DM Subjects aged 8 -15 years at enrollment with new-onset T1DM. Part 1b (study terminated prior to subject enrollment): An open-label, dose-escalation PK, PD and safety study in which participants receive 12 infusions of Aralast NP. Infusions 1 through 6 are administered at 90 mg/kg/wk and infusions 7 through 12 are administered at 180 mg/kg/wk. Part Ib consists of two groups: Subjects aged 16 - 35 years at enrollment with new-onset T1DM Subjects 8 - 15 years at enrollment with new-onset T1DM. Participants in Part Ib do not roll over into Part II (Refer to NCT01183455).

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), Diabetes Mellitus, Insulin-Dependent (new-onset), new-onset T1DM, new-onset T1D, Diabetes Mellitus, Juvenile-Onset, Diabetes, Autoimmune, Aralast NP, Alpha-1 Antitrypsin, AAT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs
Arm Type
Experimental
Arm Description
Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
Arm Title
Part 1a (Aralast NP)-Subjects 8-15 Yrs
Arm Type
Experimental
Arm Description
Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
Arm Title
Part 1b (Aralast NP)--Subjects Aged 18-35 Yrs
Arm Type
Experimental
Arm Description
Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Arm Title
Part 1b (Aralast NP)-Subjects 8-17 Yrs
Arm Type
Experimental
Arm Description
Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Intervention Type
Biological
Intervention Name(s)
Aralast NP 45 mg dose
Other Intervention Name(s)
Alpha 1-Antitrypsin, AAT
Intervention Description
- 45 mg/kg/week
Intervention Type
Biological
Intervention Name(s)
Aralast NP 90 mg dose
Other Intervention Name(s)
Alpha 1-Antitrypsin, AAT
Intervention Description
- 90 mg/kg/week
Intervention Type
Biological
Intervention Name(s)
Aralast NP 180 mg dose
Other Intervention Name(s)
Alpha-1 Antitrypsin, AAT
Intervention Description
- 180 mg/kg/week
Primary Outcome Measure Information:
Title
C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52
Description
No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks.
Time Frame
Week 52

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 T1DM within the past 100 days (of enrollment) 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: Severe active disease (chronic active hepatitis; cardiac, pulmonary disease, hepatic, renal or immunodeficiency) History of any bleeding or clotting factor deficiencies, or stroke History of vascular disease or significant vascular abnormalities Positive serology of exposure to (hepatitis B virus) HBV, HCV (hepatitis C virus), HIV (human immunodeficiency virus) or toxoplasmosis Clinically active infection with EBV (Epstein-Barr virus), CMV (cytomegalovirus), 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 T1DM or immunologic status Prior treatment with Alpha 1-Antitrypsin (Aralast NP, AAT) or hypersensitivity to alpha 1-antitrypsin 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 (immunoglobulin A) 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
RADY Children's Hospital (University of California, San Diego)
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Barbara Davis Center (University of Colorado)
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
06520
Country
United States
Facility Name
Atlanta Diabetes Associates
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Children's Hospital of Atlanta (Emory University)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa Children's Hospital
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
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 Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Naomi Berrie Diabetes Center (Columbia University)
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Pacific Northwest Research Institute-University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Participant level data and additional relevant materials are available to the public in TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
IPD Sharing Time Frame
IPD is now available in TrialShare.
IPD Sharing Access Criteria
Open to the public.
IPD Sharing URL
https://www.itntrialshare.org/project/Studies/ITN041AIPUBLIC/Study%20Data/begin.view?pageId=study.DATA_ANALYSIS
Citations:
PubMed Identifier
22634621
Citation
Ozeri E, Mizrahi M, Shahaf G, Lewis EC. alpha-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol. 2012 Jul 1;189(1):146-53. doi: 10.4049/jimmunol.1101340. Epub 2012 May 25.
Results Reference
derived
Links:
URL
https://www.niaid.nih.gov/
Description
National Institute of Allergy and Infectious Diseases (NIAID) website
URL
http://www.immunetolerance.org
Description
Immune Tolerance Network (ITN) website
URL
http://jdrf.org/about-jdrf/
Description
Juvenile Diabetes Research Foundation (JDRF)
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.itntrialshare.org/project/Studies/ITN041AIPUBLIC/Study%20Data/begin.view?pageId=study.DATA_ANALYSIS
Available IPD/Information Identifier
RETAIN ITN041AI
Available IPD/Information Comments
RETAIN ITN041AI is the Study Identifier in the Immune Tolerance Network (ITN) TrialShare Clinical Trials Research Portal

Learn more about this trial

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

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