- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00529399
Effects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects (TN08)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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California
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Los Angeles, California, United States, 90027
- Childrens Hospital of Los Angeles
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Palo Alto, California, United States, 94305
- Stanford University
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San Francisco, California, United States, 94143
- University of California-San Francisco
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Colorado
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Aurora, Colorado, United States, 80045
- Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School of Medicine
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Florida
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Gainesville, Florida, United States
- University of Florida
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Miami, Florida, United States, 33136
- University of Miami/ Miller School of Medicine
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University School of Medicine
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Joslin Diabetes Center
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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New York
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New York, New York, United States, 10032
- Columbia University
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- Childrens Hospital of Pittsburgh
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Texas
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Dallas, Texas, United States, 75390-8858
- University of Texas/Southwestern Medical School
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Washington
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Seattle, Washington, United States, 98101
- Benaroya Research Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1
3 injections of GAD-Alum vaccine
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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.
Other Names:
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Experimental: 2
2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
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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.
Other Names:
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Placebo Comparator: 3
3 injections of Aluminum hydroxide alone
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Primary Outcome is the Area Under the Stimulated C-peptide Curve (AUC) at the One Year Visit
Time Frame: Based on mixed meal tolerance test (MMTT) conducted at the one year visit
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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.
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Based on mixed meal tolerance test (MMTT) conducted at the one year visit
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Diane Wherrett, M.D., University of Toronto, Hospital for Sick Children
- Study Chair: Jay Skyler, M.D., University of Miami
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Immunologic Factors
- Gastrointestinal Agents
- Adjuvants, Immunologic
- Antacids
- Aluminum Hydroxide
- Aluminum sulfate
Other Study ID Numbers
- TN08 GAD65
- UC4DK097835 (U.S. NIH Grant/Contract)
- U01DK061055 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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