AdDIT: Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Statin Participants receive active statin and placebo ACE Inhibitor |
Drug: Statin
10mg daily for a minimum period of 2 years
Other Names:
|
| Active Comparator: Angiotensin-converting enzyme inhibitor Participants receive active ACE Inhibitor and placebo statin |
Drug: ACE inhibitor
Starting dose of 5mg daily rising after 14 days to 10mg daily providing it is well tolerated for a minimum period of 2 years.
Other Names:
|
| Placebo Comparator: Placebo Participants receive placebo ACE Inhibitor and placebo statin |
Drug: Placebo
Participants receive statin placebo and ACEI placebo
|
| Other: Combination therapy Participants receive both active ACE Inhibitor and active Statin |
Drug: Combination therapy
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Albumin creatinine ratio [2-4 years treatment duration]
The area under the curve over time of log ACR per year, with standardisation for gender, age and duration of disease
Secondary Outcome Measures
- Changes in CVD risk markers [2-4 yrs treatment duration]
Changes in measures of: cIMT, FMD, EndoPAT and PWV between baseline and the end of intervention period; arterial BP, lipids and other lipoproteins, CVD risk markers (hsCRP and ADMA), assessed every 6 months during the intervention period.
- Changes in glomerular filtration rate (GFR) [2-4 years treatment duration]
Changes in measures of GFR (plasma SDMA, creatinine adn cystatin C levels) assessed every 6 months during intervention period.
- Retinopathy [2-4 years treatment duration]
Changes in retinopathy scores and retinal microvascular structure (arteriolar or venular dilation, vascular fractile dimension, branching and tortuosity) assessed annually
- Quality of Life and Health Economics [2-4 years treatment duration]
Changes in quality of life measures and resource usage
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 10 to 16 years.
-
T1D diagnosed for more than 1 year or C-peptide negative.
-
Centralised assessment of ACR based on six early morning urines deemed to be in upper tertile for risk after adjustment for age, gender, age at diagnosis and duration of disease.
Exclusion Criteria:
-
Non T1D, i.e. type 2 diabetes, insulin dependent diabetes related to monogenic disease, secondary diabetes.
-
ACR based on six early morning urines deemed to be at low risk for subsequent development of CVD or DN.
-
Pregnancy or unwillingness to comply with contraceptive advice and regular pregnancy testing throughout the trial.
-
Breast feeding
-
Severe hyperlipidaemia and family history data to support diagnosis of familial hypercholesterolaemia.
-
Established hypertension unrelated to DN.
-
Prior exposure to the investigational products, statins and ACEI.
-
Unwillingness/inability to comply with the study protocol.
-
Other co-morbidities considered unsuitable by the investigator (excluding treated hypothyroidism and coeliac disease).
-
Proliferative retinopathy.
-
Renal disease not associated with Type 1 Diabetes.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Western Australia | Perth | Australia | ||
| 2 | Hospital for Sick Children | Toronto | Ontario | Canada |
Sponsors and Collaborators
- University of Cambridge
- Juvenile Diabetes Research Foundation
- Diabetes UK
- British Heart Foundation
- Pfizer
- The University of Western Australia
- The Hospital for Sick Children
- University of Oxford
- St Thomas' Hospital, London
Investigators
- Principal Investigator: David B Dunger, Professor, University of Cambridge
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- 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.
- 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.
- RP06
- 2007-001039-72