Back to resultsEffects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects (TN08)
Primary Purpose
Type 1 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GAD-Alum
GAD-Alum and Aluminum hydroxide
Aluminum hydroxide
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring immune tolerance, immunotherapy, antigen-specific tolerance, vaccine induced tolerance, Beta-cell function, T-cells, DPT-1, treatment of type 1 diabetes, new onset type 1 diabetes, juvenile diabetes, T1D, diabetes mellitus, Type 1 diabetes TrialNet, TrialNet
Eligibility Criteria
Inclusion Criteria:
- Age 3 to 45 years - Insulin dependent type 1-diabetes mellitus diagnosed within the previous 3 months
- Stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted 3 weeks from diagnosis of diabetes
- Presence of GAD65 antibodies
- At least one month from last immunization
- Willing to comply with intensive diabetes management
- If participant is a woman with reproductive potential, she must be willing to avoid pregnancy and have a negative pregnancy test
- Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration
Exclusion Criteria:
- Immunodeficiency or clinically significant chronic lymphopenia
- Active infection
- Positive PPD test result
- Pregnant or lactating or anticipating becoming pregnant for 24 months following first injection
- Ongoing use of medications known to influence glucose tolerance
- Require use of systemic immunosuppressant(s)
- Serologic evidence of current or past HIV, Hep B, or Hep C infection
- History of malignancies
- Ongoing use of non-insulin pharmaceuticals to affect glycemic control
- Participation in another clinical trial with a new chemical entity within the past 3 months
- Complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological, or clinically significant blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia)
- History of epilepsy, head trauma or cerebrovascular accident or clinical
- History of alcohol or drug abuse
Sites / Locations
- Childrens Hospital of Los Angeles
- Stanford University
- University of California-San Francisco
- Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center
- Yale University School of Medicine
- University of Florida
- University of Miami/ Miller School of Medicine
- Indiana University School of Medicine
- Joslin Diabetes Center
- University of Minnesota
- Columbia University
- Childrens Hospital of Pittsburgh
- University of Texas/Southwestern Medical School
- Benaroya Research Institute
- Hospital for Sick Children
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
1
2
3
Arm Description
3 injections of GAD-Alum vaccine
2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
3 injections of Aluminum hydroxide alone
Outcomes
Primary Outcome Measures
The Primary Outcome is the Area Under the Stimulated C-peptide Curve (AUC) at the One Year Visit
The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.
Secondary Outcome Measures
Full Information
NCT ID
NCT00529399
First Posted
September 12, 2007
Last Updated
April 27, 2020
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), National Center for Research Resources (NCRR), American Diabetes Association, Juvenile Diabetes Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00529399
Brief Title
Effects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects
Acronym
TN08
Official Title
Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), National Center for Research Resources (NCRR), American Diabetes Association, Juvenile Diabetes Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether treatment with multiple injections of GAD-Alum will preserve the body's own (endogenous) insulin production in patients who have been recently diagnosed with type 1 diabetes mellitus (T1DM).
Detailed Description
Type 1 diabetes (T1D) is an autoimmune disease. This means that the immune system (the part of the body which helps fight infections) mistakenly attacks and destroys the cells that produce insulin (islet cells found in the pancreas called islet cells). As these cells are destroyed, the body's ability to produce insulin decreases. Glutamic acid decarboxylase (GAD) is one of the major autoantigens (a protein that the immune system is reacting to) involved in the autoimmune process underlying T1DM.
GAD-Alum is Recombinant human (rhGAD65) and is used as an antigen-specific immune modulator. Previous studies have shown that it may slow or prevent autoimmune destruction of pancreatic islet cells by introducing "immune tolerance". By administering excess autoantigen, the body may stop its attack on its own cells that produce insulin. If the immune system's attack can be halted in a patient with recent onset T1DM, than residual insulin secretion may be maintained. This may be beneficial in decreasing acute and long-term diabetic complications as well as improving glucose control.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
Keywords
immune tolerance, immunotherapy, antigen-specific tolerance, vaccine induced tolerance, Beta-cell function, T-cells, DPT-1, treatment of type 1 diabetes, new onset type 1 diabetes, juvenile diabetes, T1D, diabetes mellitus, Type 1 diabetes TrialNet, TrialNet
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
145 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
3 injections of GAD-Alum vaccine
Arm Title
2
Arm Type
Experimental
Arm Description
2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
3 injections of Aluminum hydroxide alone
Intervention Type
Drug
Intervention Name(s)
GAD-Alum
Other Intervention Name(s)
Diamyd
Intervention Description
Participants will receive 3 injections of 20 micrograms GAD-Alum subcutaneously. The first two injections are given 4 weeks apart and the second and third are given 8 weeks apart.
Intervention Type
Drug
Intervention Name(s)
GAD-Alum and Aluminum hydroxide
Other Intervention Name(s)
Diamyd
Intervention Description
Participants will receive 3 injections subcutaneously. The first two will contain 20 micrograms GAD-Alum vaccine and are given 4 weeks apart. The third injection will be Aluminum hydroxide alone and will be given 8 weeks after the second injection.
Intervention Type
Drug
Intervention Name(s)
Aluminum hydroxide
Other Intervention Name(s)
Alhydrogel
Intervention Description
Participants will receive 3 injections of Aluminum hydroxide alone, subcutaneously. The first two injections are given 4 weeks apart and the second and third are given 8 weeks apart.
Primary Outcome Measure Information:
Title
The Primary Outcome is the Area Under the Stimulated C-peptide Curve (AUC) at the One Year Visit
Description
The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.
Time Frame
Based on mixed meal tolerance test (MMTT) conducted at the one year visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 3 to 45 years - Insulin dependent type 1-diabetes mellitus diagnosed within the previous 3 months
Stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted 3 weeks from diagnosis of diabetes
Presence of GAD65 antibodies
At least one month from last immunization
Willing to comply with intensive diabetes management
If participant is a woman with reproductive potential, she must be willing to avoid pregnancy and have a negative pregnancy test
Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration
Exclusion Criteria:
Immunodeficiency or clinically significant chronic lymphopenia
Active infection
Positive PPD test result
Pregnant or lactating or anticipating becoming pregnant for 24 months following first injection
Ongoing use of medications known to influence glucose tolerance
Require use of systemic immunosuppressant(s)
Serologic evidence of current or past HIV, Hep B, or Hep C infection
History of malignancies
Ongoing use of non-insulin pharmaceuticals to affect glycemic control
Participation in another clinical trial with a new chemical entity within the past 3 months
Complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological, or clinically significant blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia)
History of epilepsy, head trauma or cerebrovascular accident or clinical
History of alcohol or drug abuse
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diane Wherrett, M.D.
Organizational Affiliation
University of Toronto, Hospital for Sick Children
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jay Skyler, M.D.
Organizational Affiliation
University of Miami
Official's Role
Study Chair
Facility Information:
Facility Name
Childrens Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of California-San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
University of Miami/ Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Joslin Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Childrens Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas/Southwestern Medical School
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8858
Country
United States
Facility Name
Benaroya Research Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn08-gad-new-onset/?query=tn08
IPD Sharing URL
https://repository.niddk.nih.gov/studies/tn08-gad-new-onset/?query=tn08
Citations:
PubMed Identifier
11476858
Citation
Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001 Jul 21;358(9277):221-9. doi: 10.1016/S0140-6736(01)05415-0. Erratum In: Lancet. 2001 Sep 1;358(9283):766.
Results Reference
background
PubMed Identifier
7606872
Citation
Pleau JM, Fernandez-Saravia F, Esling A, Homo-Delarche F, Dardenne M. Prevention of autoimmune diabetes in nonobese diabetic female mice by treatment with recombinant glutamic acid decarboxylase (GAD 65). Clin Immunol Immunopathol. 1995 Jul;76(1 Pt 1):90-5. doi: 10.1006/clin.1995.1092.
Results Reference
background
PubMed Identifier
8946834
Citation
Tian J, Clare-Salzler M, Herschenfeld A, Middleton B, Newman D, Mueller R, Arita S, Evans C, Atkinson MA, Mullen Y, Sarvetnick N, Tobin AJ, Lehmann PV, Kaufman DL. Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. Nat Med. 1996 Dec;2(12):1348-53. doi: 10.1038/nm1296-1348.
Results Reference
background
PubMed Identifier
9604865
Citation
Tisch R, Liblau RS, Yang XD, Liblau P, McDevitt HO. Induction of GAD65-specific regulatory T-cells inhibits ongoing autoimmune diabetes in nonobese diabetic mice. Diabetes. 1998 Jun;47(6):894-9. doi: 10.2337/diabetes.47.6.894.
Results Reference
background
PubMed Identifier
11160264
Citation
Tisch R, Wang B, Weaver DJ, Liu B, Bui T, Arthos J, Serreze DV. Antigen-specific mediated suppression of beta cell autoimmunity by plasmid DNA vaccination. J Immunol. 2001 Feb 1;166(3):2122-32. doi: 10.4049/jimmunol.166.3.2122.
Results Reference
background
PubMed Identifier
12107747
Citation
Jun HS, Chung YH, Han J, Kim A, Yoo SS, Sherwin RS, Yoon JW. Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase. Diabetologia. 2002 May;45(5):668-76. doi: 10.1007/s00125-002-0806-9. Epub 2002 Apr 4.
Results Reference
background
PubMed Identifier
21714999
Citation
Wherrett DK, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Herold KC, Marks JB, Monzavi R, Moran A, Orban T, Palmer JP, Raskin P, Rodriguez H, Schatz D, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet GAD Study Group. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet. 2011 Jul 23;378(9788):319-27. doi: 10.1016/S0140-6736(11)60895-7. Epub 2011 Jun 27.
Results Reference
result
Links:
URL
http://www.diabetestrialnet.org/
Description
Related Info
URL
http://www.jdrf.org
Description
Related Info
Learn more about this trial
Effects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects
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