Effects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects
TN08
3 other identifiers
interventional
145
2 countries
15
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2009
Typical duration for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 12, 2007
CompletedFirst Posted
Study publicly available on registry
September 14, 2007
CompletedStudy Start
First participant enrolled
February 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2012
CompletedResults Posted
Study results publicly available
December 7, 2016
CompletedMay 7, 2020
April 1, 2020
3.2 years
September 12, 2007
May 12, 2016
April 27, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Based on mixed meal tolerance test (MMTT) conducted at the one year visit
Study Arms (3)
1
EXPERIMENTAL3 injections of GAD-Alum vaccine
2
EXPERIMENTAL2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
3
PLACEBO COMPARATOR3 injections of Aluminum hydroxide alone
Interventions
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)lead
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)collaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
- National Center for Research Resources (NCRR)collaborator
- American Diabetes Associationcollaborator
- Juvenile Diabetes Research Foundationcollaborator
Study Sites (15)
Childrens Hospital of Los Angeles
Los Angeles, California, 90027, United States
Stanford University
Palo Alto, California, 94305, United States
University of California-San Francisco
San Francisco, California, 94143, United States
Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center
Aurora, Colorado, 80045, United States
Yale University School of Medicine
New Haven, Connecticut, 06520, United States
University of Florida
Gainesville, Florida, United States
University of Miami/ Miller School of Medicine
Miami, Florida, 33136, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
Joslin Diabetes Center
Boston, Massachusetts, 02215, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Columbia University
New York, New York, 10032, United States
Childrens Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
University of Texas/Southwestern Medical School
Dallas, Texas, 75390-8858, United States
Benaroya Research Institute
Seattle, Washington, 98101, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (7)
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.
PMID: 11476858BACKGROUNDPleau 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.
PMID: 7606872BACKGROUNDTian 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.
PMID: 8946834BACKGROUNDTisch 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.
PMID: 9604865BACKGROUNDTisch 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.
PMID: 11160264BACKGROUNDJun 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.
PMID: 12107747BACKGROUNDWherrett 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.
PMID: 21714999RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Carla Greenbaum
- Organization
- Benaroya Research Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Diane Wherrett, M.D.
University of Toronto, Hospital for Sick Children
- STUDY CHAIR
Jay Skyler, M.D.
University of Miami
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 12, 2007
First Posted
September 14, 2007
Study Start
February 1, 2009
Primary Completion
May 1, 2012
Study Completion
May 1, 2012
Last Updated
May 7, 2020
Results First Posted
December 7, 2016
Record last verified: 2020-04
Data Sharing
- IPD Sharing
- Will share
Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn08-gad-new-onset/?query=tn08