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The study was interrupted early and terminated when only 26 out of 80 patients were enrolled due to new clinical study results indicating that the current study would not be informative.
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| Name | Class |
|---|---|
| Region Skane | OTHER |
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The purpose of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), in combination with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes in non-diabetic children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.
The primary objective of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), combined with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes (diagnosed according to American Diabetes Association criteria) in non-diabetic 4-17.99 year old children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.
The secondary objective is to demonstrate that treatment with Diamyd is safe in children at risk for type 1 diabetes.
The children will be followed for 5 years in the study. Primary endpoint is proportion of subjects diagnosed with type 1 diabetes in each treatment arm. Secondary endpoints are 1) safety, 2) change in metabolic status from normal to impaired glucose metabolism in the group of children with normal glucose metabolism at baseline screening.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alum-GAD, Vitamin D3 | Experimental | Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years. |
|
| Placebo, Vitamin D3 | Placebo Comparator | Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alum-GAD | Drug | Two doses à 20 microgram 30 days apart subcutaneously administrated |
|
| Measure | Description | Time Frame |
|---|---|---|
| Type 1 Diabetes Month 24 | Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm month 24 | 24 months |
| Type 1 Diabetes Status Overall | Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm overall. Including one patient diagnosed shortly after the month 24 visit. | Over the entire study period up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Developing Impaired Glucose Metabolism Until Month 18 | Change in metabolic status from normal to impaired glucose metabolism during follow-up in the group of children with normal glucose metabolism at baseline screening. Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Helena Elding Larsson, MD, PhD | Lund University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11 | Malmö | 205 02 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25381193 | Background | Elding Larsson H, Larsson C, Lernmark A; DiAPREV-IT study group. Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention. Acta Diabetol. 2015 Jun;52(3):473-81. doi: 10.1007/s00592-014-0680-1. Epub 2014 Nov 8. | |
| 23469940 | Background | Andersson C, Carlsson A, Cilio C, Cedervall E, Ivarsson SA, Jonsdottir B, Jonsson B, Larsson K, Neiderud J, Lernmark A, Elding Larsson H; DiAPREV-IT Study Group. Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study. Pediatr Diabetes. 2013 Aug;14(5):341-9. doi: 10.1111/pedi.12023. Epub 2013 Mar 8. |
| Label | URL |
|---|---|
| Link to the description of the first DiAPREV-IT study, that have included 50 children and is still ongoing | View source |
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29 patients were screened for the study and 26 entered the study. Three patients were screening failures.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alum-GAD, Vitamin D3 | Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years. Alum-GAD (Glutamic Acid Decarboxylase): Two doses à 20 microgram 30 days apart subcutaneously administrated Vitamin D3: 2000 Units (IE) (50 microgram) vitamin D3 daily |
| FG001 | Placebo, Vitamin D3 | Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years Vitamin D3: 2000 Units (IE) (50 microgram) vitamin D3 daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Alum-GAD, Vitamin D3 | Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years. Alum-GAD: Two doses à 20 microgram 30 days apart subcutaneously administrated Vitamin D3: 2000 Units (IE) (50 microgram) vitamin D3 daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Type 1 Diabetes Month 24 | Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm month 24 | Posted | Count of Participants | Participants | 24 months |
|
During the entire study period approximately 24 months.
At each study visit the investigator asked for any adverse events and recorded them in the CRF (Case Report Form).
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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 | Alum-GAD, Vitamin D3 | Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years. Alum-GAD: Two doses à 20 microgram 30 days apart subcutaneously administrated Vitamin D3: 2000 Units (IE) (50 microgram) vitamin D3 daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Limb injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
This study was interrupted early and terminated when only 26 out of 80 patients were enrolled. The patients were followed for 2 years rather than the planned 5 years.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Helena Elding Larsson | Skåne University Hospital | +4640337676 | helena.larsson@med.lu.se |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 28, 2017 | Sep 1, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 5, 2020 | Sep 1, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Vitamin D3 | Drug | 2000 Units (IE) (50 microgram) vitamin D3 daily |
|
|
| During 18 months follow-up |
| Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18 | Number of patients who have progression from already impaired glucose metabolism from one or several criteria to additional signs of reduced glucose metabolism (within children with impaired glucose metabolism at screening). Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more. | During 18 months follow-up |
| Injection Site Reactions Day 1 | Number of patients experiencing injection site reactions at day 1 | Day 1 |
| Injection Site Reactions Month 1 | Number of patients experiencing injection site reactions at month 1 | Month 1 |
| Change From Baseline in GADA Month 1 | Change from baseline to month 1 in GADA (Glutamic Acid Decarboxylase Antibodies) titers | Month 1 |
| Change From Baseline in GADA Month 12 | Change from baseline to month 12 in GADA titers | Month 12 |
| Change From Baseline in GADA Month 24 | Change from baseline to month 24 in GADA titers | Month 24 |
| 22296077 | Background | Ludvigsson J, Krisky D, Casas R, Battelino T, Castano L, Greening J, Kordonouri O, Otonkoski T, Pozzilli P, Robert JJ, Veeze HJ, Palmer J, Samuelsson U, Elding Larsson H, Aman J, Kardell G, Neiderud Helsingborg J, Lundstrom G, Albinsson E, Carlsson A, Nordvall M, Fors H, Arvidsson CG, Edvardson S, Hanas R, Larsson K, Rathsman B, Forsgren H, Desaix H, Forsander G, Nilsson NO, Akesson CG, Keskinen P, Veijola R, Talvitie T, Raile K, Kapellen T, Burger W, Neu A, Engelsberger I, Heidtmann B, Bechtold S, Leslie D, Chiarelli F, Cicognani A, Chiumello G, Cerutti F, Zuccotti GV, Gomez Gila A, Rica I, Barrio R, Clemente M, Lopez Garcia MJ, Rodriguez M, Gonzalez I, Lopez JP, Oyarzabal M, Reeser HM, Nuboer R, Stouthart P, Bratina N, Bratanic N, de Kerdanet M, Weill J, Ser N, Barat P, Bertrand AM, Carel JC, Reynaud R, Coutant R, Baron S. GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med. 2012 Feb 2;366(5):433-42. doi: 10.1056/NEJMoa1107096. |
| BG001 | Placebo, Vitamin D3 | Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years Vitamin D3: 2000 Units (IE) (50 microgram) vitamin D3 daily |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Celiac disease | Count of Participants | Participants |
|
| Thyroid disease | Count of Participants | Participants |
|
| Relatedness | Count of Participants | Participants |
|
|
|
| Primary | Type 1 Diabetes Status Overall | Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm overall. Including one patient diagnosed shortly after the month 24 visit. | Posted | Count of Participants | Participants | Over the entire study period up to 2 years |
|
|
|
| Secondary | Number of Patients Developing Impaired Glucose Metabolism Until Month 18 | Change in metabolic status from normal to impaired glucose metabolism during follow-up in the group of children with normal glucose metabolism at baseline screening. Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more. | Only patients with normal glucose at baseline and glucose measured at month 18 are included. | Posted | Count of Participants | Participants | During 18 months follow-up |
|
|
|
| Secondary | Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18 | Number of patients who have progression from already impaired glucose metabolism from one or several criteria to additional signs of reduced glucose metabolism (within children with impaired glucose metabolism at screening). Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more. | Only patients with impaired glucose at baseline and glucose measured at month 18 are included. | Posted | Count of Participants | Participants | During 18 months follow-up |
|
|
|
| Secondary | Injection Site Reactions Day 1 | Number of patients experiencing injection site reactions at day 1 | Posted | Number | participants | Day 1 |
|
|
|
| Secondary | Injection Site Reactions Month 1 | Number of patients experiencing injection site reactions at month 1 | Posted | Number | participants | Month 1 |
|
|
|
| Secondary | Change From Baseline in GADA Month 1 | Change from baseline to month 1 in GADA (Glutamic Acid Decarboxylase Antibodies) titers | Only patients with GADA measured both at baseline and month 1 are included. | Posted | Mean | Standard Deviation | U/mL | Month 1 |
|
|
|
| Secondary | Change From Baseline in GADA Month 12 | Change from baseline to month 12 in GADA titers | Only patients with GADA measured at baseline and at month 12 are included. | Posted | Mean | Standard Deviation | U/mL | Month 12 |
|
|
|
| Secondary | Change From Baseline in GADA Month 24 | Change from baseline to month 24 in GADA titers | Only patients with GADA measured at baseline and month 24 are included. | Posted | Mean | Standard Deviation | U/mL | Month 24 |
|
|
|
| 0 |
| 13 |
| 1 |
| 13 |
| 12 |
| 13 |
| EG001 | Placebo, Vitamin D3 | Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years Vitamin D3: 2000 Units (IE) (50 microgram) vitamin D3 daily | 0 | 13 | 1 | 13 | 12 | 13 |
| Post streptococcal glomerulonephritis | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Enterobiasis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Febrile infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Growing pains | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Attention deficit/hyperactivit | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
|
Not provided
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| Itching |
|
| Oedema |
|
| Pain |
|
| Tenderness |
|
| Itching |
|
| Oedema |
|
| Pain |
|
| Tenderness |
|