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| ID | Type | Description | Link |
|---|---|---|---|
| U01DK061055 | U.S. NIH Grant/Contract | View source | |
| UC4DK097835 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| National Center for Research Resources (NCRR) |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | 3 injections of GAD-Alum vaccine |
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| 2 | Experimental | 2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone |
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| 3 | Placebo Comparator | 3 injections of Aluminum hydroxide alone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GAD-Alum | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diane Wherrett, M.D. | University of Toronto, Hospital for Sick Children | Principal Investigator |
| Jay Skyler, M.D. | University of Miami | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens Hospital of Los Angeles | Los Angeles | California | 90027 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11476858 | Background | 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. | |
| 7606872 | Background | 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. |
| Label | URL |
|---|---|
| Related Info | View source |
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Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn08-gad-new-onset/?query=tn08
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The original recruitment goal was to enroll 126 subjects. However, additional eligible subjects were identified during the screening process and 145 subjects were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | GAD-alum | 3 injections of Glutamic Acid Decarboxylase (GAD)-Alum vaccine GAD-Alum: 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. |
| FG001 | GAD-alum Plus Alum |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| American Diabetes Association | OTHER |
| Juvenile Diabetes Research Foundation | OTHER |
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|
| GAD-Alum and Aluminum hydroxide | Drug | 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. |
|
|
| Aluminum hydroxide | Drug | 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. |
|
|
| 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 |
| 8946834 | Background | 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. |
| 9604865 | Background | 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. |
| 11160264 | Background | 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. |
| 12107747 | Background | 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. |
| 21714999 | Result | 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. |
| Related Info | View source |
2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone GAD-Alum: 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. |
| FG002 | Alum Alone | 3 injections of Aluminum hydroxide alone Aluminum hydroxide: 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | GAD-alum | 3 injections of GAD-Alum vaccine GAD-Alum: 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. |
| BG001 | GAD-alum Plus Alum | 2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone GAD-Alum: 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. |
| BG002 | Alum Alone | 3 injections of Aluminum hydroxide alone Aluminum hydroxide: 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Geometric Mean | 95% Confidence Interval | nmol/L | Based on mixed meal tolerance test (MMTT) conducted at the one year visit |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GAD-alum | 3 injections of GAD-Alum vaccine GAD-Alum: 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. | 5 | 48 | 20 | 48 | ||
| EG001 | GAD-alum Plus Alum | 2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone GAD-Alum: 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. | 3 | 49 | 25 | 49 | ||
| EG002 | Alum Alone | 3 injections of Aluminum hydroxide alone Aluminum hydroxide: 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. | 5 | 48 | 24 | 48 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac ischemia/infarction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Endocrine - Other | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Infection - Other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphatics - Other | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Acidosis (metabolic or respiratory) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Glucose, serum-low (hypoglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fracture | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neurology - Other | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Personality/behavioral | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Intra-operative Injury - Other | Surgical and medical procedures | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Auditory/Ear- Other | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Injection site reaction/extravasation changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Endocrine - Other | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Infection - Other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| Sinus Infection with unknown ANC | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| Musculoskeletal/Soft Tissue - Other | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pain- Abdomen NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pain - Other | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pulmonary/Upper Respiratory - Other | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carla Greenbaum | Benaroya Research Institute | cjgreen@benaroyaresearch.org |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000536 | Aluminum Hydroxide |
| ID | Term |
|---|---|
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D017607 | Aluminum Compounds |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
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| Male |
|
The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis. |
| ANCOVA |
| 0.51 |
| Superiority or Other (legacy) |