Type 1 Diabetes
Conditions
Keywords
Adolescence
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.
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.
Interventions
DRUGStatin
10mg daily for a minimum period of 2 years
DRUGACE 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.
DRUGPlacebo
Participants receive statin placebo and ACEI placebo
DRUGCombination 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.
Sponsors
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
University of Cambridge
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Age 10 to 16 years. 2. T1D diagnosed for more than 1 year or C-peptide negative. 3. 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
1. Non T1D, i.e. type 2 diabetes, insulin dependent diabetes related to monogenic disease, secondary diabetes. 2. ACR based on six early morning urines deemed to be at low risk for subsequent development of CVD or DN. 3. Pregnancy or unwillingness to comply with contraceptive advice and regular pregnancy testing throughout the trial. 4. Breast feeding 5. Severe hyperlipidaemia and family history data to support diagnosis of familial hypercholesterolaemia. 6. Established hypertension unrelated to DN. 7. Prior exposure to the investigational products, statins and ACEI. 8. Unwillingness/inability to comply with the study protocol. 9. Other co-morbidities considered unsuitable by the investigator (excluding treated hypothyroidism and coeliac disease). 10. Proliferative retinopathy. 11. Renal disease not associated with Type 1 Diabetes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in CVD risk markers | 2-4 yrs treatment duration | Changes in measures of: 1. cIMT, FMD, EndoPAT and PWV between baseline and the end of intervention period; 2. 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 |
Countries
Australia, Canada
Outcome results
None listed