{"id":"ddbf6c1c-653c-52d3-b55e-414ddb116126","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-targeting-the-autoantigen-did-not-work","predicate":"preserves_measured_pool","statement":"We studied 334 patients aged 10 to 20 years with type 1 diabetes, fasting C-peptide levels of more than 0.3 nanograms per millilitre and detectable serum GAD65 autoantibodies, randomly assigned within 3 months after diagnosis to four doses of GAD-alum, two doses followed by two doses of placebo, or four doses of placebo, the stimulated C-peptide level declined to a similar degree in all study groups and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group with P = 0.10, and the use of GAD-alum did not affect the insulin dose, glycated haemoglobin level or hypoglycaemia rate.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"67359a48-bfd3-5c0f-917c-830c9069368b","mechanism_event_label":"Vaccinating against the enzyme the immune system attacks did not slow the loss of insulin production.","subject":{"id":"9fc0cb17-fe45-5145-b314-d33c53b2df51","slug":"gad-alum","display_name":"Alum-formulated GAD65 antigen therapy","entity_type_key":"drug"},"object":{"id":"96571558-80ac-5c99-8674-5eb3189bb57c","slug":"stimulated-c-peptide","display_name":"Stimulated serum C-peptide after a mixed-meal tolerance test","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"67359a48-bfd3-5c0f-917c-830c9069368b","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-targeting-the-autoantigen-did-not-work-event","event_type":"observed_intervention","label":"Vaccinating against the enzyme the immune system attacks did not slow the loss of insulin production.","description":"We studied 334 patients aged 10 to 20 years with type 1 diabetes, fasting C-peptide levels of more than 0.3 nanograms per millilitre and detectable serum GAD65 autoantibodies, randomly assigned within 3 months after diagnosis to four doses of GAD-alum, two doses followed by two doses of placebo, or four doses of placebo, the stimulated C-peptide level declined to a similar degree in all study groups and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group with P = 0.10, and the use of GAD-alum did not affect the insulin dose, glycated haemoglobin level or hypoglycaemia rate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"539904ca-6f1a-5fa7-a5a0-015909913886","slug":"gad65","display_name":"Glutamate decarboxylase 65 / GAD2","entity_type_key":"protein"},"role":"targeted_autoantigen","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"64e9f845-04c2-54c5-bdaa-14eda8260c4a","slug":"type-1-diabetes","display_name":"Type 1 diabetes","entity_type_key":"cellular_process"},"role":"studied_condition","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"66709f33-8eeb-5618-b262-023a13db02ad","slug":"islet-beta-cell","display_name":"Pancreatic islet beta cell","entity_type_key":"cell_type"},"role":"protected_cell","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9fc0cb17-fe45-5145-b314-d33c53b2df51","slug":"gad-alum","display_name":"Alum-formulated GAD65 antigen therapy","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"96571558-80ac-5c99-8674-5eb3189bb57c","slug":"stimulated-c-peptide","display_name":"Stimulated serum C-peptide after a mixed-meal tolerance test","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/gaba-research/22296077.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"fc3bf9a083b3179c8573e993fb61f09412eca7890c3ccfb3ba5b8c0fb26acce8\", \"start_char\": 0, \"end_char\": 1683, \"text_sha256\": \"fc3bf9a083b3179c8573e993fb61f09412eca7890c3ccfb3ba5b8c0fb26acce8\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomised placebo-controlled trial of an alum-formulated autoantigen in 334 patients within three months of diagnosis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Four doses of GAD-alum, two doses followed by placebo, or four doses of placebo, in patients aged 10 to 20 with detectable GAD65 autoantibodies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A properly powered randomised trial with stimulated C-peptide as the primary outcome. It tests the autoantigen as a therapy, not GABA.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in.","comparator":null,"unit":null,"notes":"","entity":{"slug":"gaba","display_name":"Gamma-aminobutyric acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Vaccinating against the enzyme the immune system attacks did not slow the loss of insulin production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[gb-p22296077] GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. (2012). https://pubmed.ncbi.nlm.nih.gov/22296077/ DOI: 10.1056/nejmoa1107096","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Pancreatic beta cell function","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"760e645b-c2eb-54ff-8b7d-ba14c2be2ec3","evidence_kind":"source_excerpt","locator":"Lines 456-467","start_line":456,"end_line":467,"excerpt":"### gb-targeting-the-autoantigen-did-not-work\nWe studied 334 patients aged 10 to 20 years with type 1 diabetes, fasting C-peptide levels of more than 0.3 nanograms per millilitre and detectable serum GAD65 autoantibodies, randomly assigned within 3 months after diagnosis to four doses of GAD-alum, two doses followed by two doses of placebo, or four doses of placebo, the stimulated C-peptide level declined to a similar degree in all study groups and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group with P = 0.10, and the use of GAD-alum did not affect the insulin dose, glycated haemoglobin level or hypoglycaemia rate.\nCondition category: normal\nnutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in.\nplain_language: Vaccinating against the enzyme the immune system attacks did not slow the loss of insulin production.\norganism: Human\ntissue_or_cell_type: Pancreatic beta cell function\nexperimental_model: Randomised placebo-controlled trial of an alum-formulated autoantigen in 334 patients within three months of diagnosis\nlimitations: A properly powered randomised trial with stimulated C-peptide as the primary outcome. It tests the autoantigen as a therapy, not GABA.\nexposure: Four doses of GAD-alum, two doses followed by placebo, or four doses of placebo, in patients aged 10 to 20 with detectable GAD65 autoantibodies\nevidence_span: {\"source_cache\": \"artifacts/gaba-research/22296077.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"fc3bf9a083b3179c8573e993fb61f09412eca7890c3ccfb3ba5b8c0fb26acce8\", \"start_char\": 0, \"end_char\": 1683, \"text_sha256\": \"fc3bf9a083b3179c8573e993fb61f09412eca7890c3ccfb3ba5b8c0fb26acce8\"}\n[gb-p22296077] GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. 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