Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)

University of Cambridge

Status and phase: Completed; Phase 3

Conditions: Type 1 Diabetes

Treatments: Drug: Combination therapy; Drug: Placebo; Drug: Statin; Drug: ACE inhibitor

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01581476

RP06

2007-001039-72 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 443 patients

Sex: All

Ages: 10 to 16 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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443 participants in 4 patient groups, including a placebo group

Statin

Active Comparator group

Description:

Participants receive active statin and placebo ACE Inhibitor

Treatment:

Drug: Statin

Angiotensin-converting enzyme inhibitor

Active Comparator group

Description:

Participants receive active ACE Inhibitor and placebo statin

Treatment:

Drug: ACE inhibitor

Placebo

Placebo Comparator group

Description:

Participants receive placebo ACE Inhibitor and placebo statin

Treatment:

Drug: Placebo

Combination therapy

Other group

Description:

Participants receive both active ACE Inhibitor and active Statin

Treatment:

Drug: Combination therapy