Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial

Phase 3

Completed

• Conditions: Type 1 Diabetes
• Interventions: Drug: Statin; Drug: Placebo; Drug: Combination therapy; Drug: ACE inhibitor

• Registration Number: NCT01581476
• Lead Sponsor: University of Cambridge

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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2012-04-13
• Study First Submitted QC: 2012-04-19
• Study First Posted: 2012-04-20
• Primary Completion: 2017-04
• Study Completion: 2017-06
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-26
• Last Update Posted: 2018-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 443

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Statin	Statin	Participants receive active statin and placebo ACE Inhibitor
Placebo	Placebo	Participants receive placebo ACE Inhibitor and placebo statin
Combination therapy	Combination therapy	Participants receive both active ACE Inhibitor and active Statin
Angiotensin-converting enzyme inhibitor	ACE inhibitor	Participants receive active ACE Inhibitor and placebo statin

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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.

Trial Locations

Locations (2)

University of Western Australia; 🇦🇺 Perth, Australia

Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada