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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-001039-72 | EudraCT Number |
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| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
| Diabetes UK | OTHER |
| British Heart Foundation | OTHER |
| Pfizer |
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The purpose of this study is to determine whether use of blood pressure lowering drugs, Angiotensin converting enzyme inhibitors (ACEIs) and blood fat (lipid) lowering drugs (statins) may have a place in the treatment of adolescents with diabetes and can help reduce serious long-term health problems in this population.
Subjects will be recruited from a pre-screened population of 3,000 young people with T1D aged 10 to 16 years based on assessment of risk for future CVD and DN.
They will be randomised to a 2 x 2 factorial design contrasting the effects of ACEI, statins, or combination therapy to placebo over a maximum four year treatment period. Minimisation of variation in albumin excretion rate, gender, age, diabetes duration, HbA1c, total cholesterol and centre site will be undertaken at randomisation.
Analysis of the primary endpoint, change in albumin excretion will be undertaken on an intention to treat basis. Secondary analyses will be undertaken on the basis of 'as treated' allowing for variance in compliance and allowing for subjects who show substantial change in HbA1c levels. Additional analyses will be undertaken to assess changes in the secondary objectives and to assess the overall effect of the intervention on quality of life and health economics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Statin | Active Comparator | Participants receive active statin and placebo ACE Inhibitor |
|
| Angiotensin-converting enzyme inhibitor | Active Comparator | Participants receive active ACE Inhibitor and placebo statin |
|
| Placebo | Placebo Comparator | Participants receive placebo ACE Inhibitor and placebo statin |
|
| Combination therapy | Other | Participants receive both active ACE Inhibitor and active Statin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Statin | Drug | 10mg daily for a minimum period of 2 years |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Albumin creatinine ratio | The area under the curve over time of log ACR per year, with standardisation for gender, age and duration of disease | 2-4 years treatment duration |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in CVD risk markers | Changes in measures of:
| 2-4 yrs treatment duration |
| Changes in glomerular filtration rate (GFR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David B Dunger, Professor | University of Cambridge | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Western Australia | Perth | Australia | ||||
| Hospital for Sick Children |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18349042 | Background | Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008 Mar 29;336(7646):697-701. doi: 10.1136/bmj.39478.378241.BE. Epub 2008 Mar 18. | |
| 17257274 |
| Label | URL |
|---|---|
| Click here for information about the Adolescent Type 1 Diabetes Cardio Renal Intervention Trial (AdDIT) | View source |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D019161 | Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| D000069059 | Atorvastatin |
| D000806 | Angiotensin-Converting Enzyme Inhibitors |
| D000077583 | Quinapril |
| D003131 | Combined Modality Therapy |
| ID | Term |
|---|---|
| D000924 | Anticholesteremic Agents |
| D000960 | Hypolipidemic Agents |
| D000963 | Antimetabolites |
| D045504 | Molecular Mechanisms of Pharmacological Action |
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| INDUSTRY |
| The University of Western Australia | OTHER |
| The Hospital for Sick Children | OTHER |
| University of Oxford | OTHER |
| St Thomas' Hospital, London | OTHER |
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| ACE inhibitor | Drug | Starting dose of 5mg daily rising after 14 days to 10mg daily providing it is well tolerated for a minimum period of 2 years. |
|
|
| Placebo | Drug | Participants receive statin placebo and ACEI placebo |
|
| Combination therapy | Drug | Participants receive both active statin and active ACEI. Dose for Statins is 10mg daily. Dosing for ACEI starts at 5mg daily rising to 10mg after 14 days providing it is well tolerated. Both interventions last for a minimum of 2 years. |
|
|
Changes in measures of GFR (plasma SDMA, creatinine adn cystatin C levels) assessed every 6 months during intervention period. |
| 2-4 years treatment duration |
| Retinopathy | Changes in retinopathy scores and retinal microvascular structure (arteriolar or venular dilation, vascular fractile dimension, branching and tortuosity) assessed annually | 2-4 years treatment duration |
| Quality of Life and Health Economics | Changes in quality of life measures and resource usage | 2-4 years treatment duration |
| Toronto |
| Ontario |
| Canada |
| Dunger DB, Schwarze CP, Cooper JD, Widmer B, Neil HA, Shield J, Edge JA, Jones TW, Daneman D, Dalton RN. Can we identify adolescents at high risk for nephropathy before the development of microalbuminuria? Diabet Med. 2007 Feb;24(2):131-6. doi: 10.1111/j.1464-5491.2006.02047.x. |
| 20017932 | Background | Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group. Adolescent type 1 Diabetes Cardio-renal Intervention Trial (AdDIT). BMC Pediatr. 2009 Dec 17;9:79. doi: 10.1186/1471-2431-9-79. |
| 22416821 | Result | Cherney DZ, Scholey JW, Daneman D, Dunger DB, Dalton RN, Moineddin R, Mahmud FH, Dekker R, Elia Y, Sochett E, Reich HN. Urinary markers of renal inflammation in adolescents with Type 1 diabetes mellitus and normoalbuminuria. Diabet Med. 2012 Oct;29(10):1297-302. doi: 10.1111/j.1464-5491.2012.03651.x. |
| 42056188 | Derived | Prampolini B, Giton A, Frassineti S, Benitez-Aguirre P, Cameron FJ, Craig ME, Couper JJ, Dalton RN, Daneman D, Davis EA, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HA, Deanfield JE, Marcovecchio ML, Chiesa ST. Effect of statins and ACE inhibitors on the metabolome in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) cohort. Sci Rep. 2026 Apr 29. doi: 10.1038/s41598-026-50044-w. Online ahead of print. |
| 38124088 | Derived | Mahmud FH, Clarke ABM, Elia Y, Curtis J, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Clarson C, Couper JJ, Craig ME, Dalton RN, Daneman D, Davis EA, Deanfield JE, Donaghue KC, Jones TW, Marshall SM, Neil A, Marcovecchio ML. Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data. BMC Med. 2023 Dec 20;21(1):506. doi: 10.1186/s12916-023-03222-w. |
| 33100044 | Derived | Chiesa ST, Marcovecchio ML, Benitez-Aguirre P, Cameron FJ, Craig ME, Couper JJ, Davis EA, Dalton RN, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, Deanfield JE; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group. Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes. Hypertension. 2020 Dec;76(6):1734-1743. doi: 10.1161/HYPERTENSIONAHA.120.15721. Epub 2020 Oct 26. |
| 32108022 | Derived | Niechcial E, Acerini CL, Chiesa ST, Stevens T, Dalton RN, Daneman D, Deanfield JE, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, Marcovecchio ML; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group; Adolescent Type 1 Diabetes Cardio-renal Intervention Trial AdDIT Study Group. Medication Adherence During Adjunct Therapy With Statins and ACE Inhibitors in Adolescents With Type 1 Diabetes. Diabetes Care. 2020 May;43(5):1070-1076. doi: 10.2337/dc19-0884. Epub 2020 Feb 27. |
| 29091568 | Derived | Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB; AdDIT Study Group. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med. 2017 Nov 2;377(18):1733-1745. doi: 10.1056/NEJMoa1703518. |
| 25392936 | Derived | Har RL, Reich HN, Scholey JW, Daneman D, Dunger DB, Moineddin R, Dalton RN, Motran L, Elia Y, Deda L, Ostrovsky M, Sochett EB, Mahmud FH, Cherney DZ. The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes. PLoS One. 2014 Nov 13;9(11):e111131. doi: 10.1371/journal.pone.0111131. eCollection 2014. |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D004791 | Enzyme Inhibitors |
| D057847 | Lipid Regulating Agents |
| D045506 | Therapeutic Uses |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D011480 | Protease Inhibitors |
| D044005 | Tetrahydroisoquinolines |
| D007546 | Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D013812 | Therapeutics |