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

June 26, 2018 updated by: David Dunger, University of Cambridge

Randomised, Double Blind, Placebo Controlled Trial of Angiotensin Converting Enzyme Inhibitors and Statins in the Prevention of Long Term Complications in Young People With Type 1 Diabetes

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

443

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Perth, Australia
        • University of Western Australia
  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Hospital for Sick Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 16 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / 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:
  • Atorvastatin
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:
  • Quinapril
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:
  • Atorvastatin
  • Quinapril

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Albumin creatinine ratio
Time Frame: 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
2-4 years treatment duration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in CVD risk markers
Time Frame: 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.
2-4 yrs treatment duration
Changes in glomerular filtration rate (GFR)
Time Frame: 2-4 years treatment duration
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
Time Frame: 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
2-4 years treatment duration
Quality of Life and Health Economics
Time Frame: 2-4 years treatment duration
Changes in quality of life measures and resource usage
2-4 years treatment duration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cambridge

Collaborators

The Hospital for Sick Children
Pfizer
Juvenile Diabetes Research Foundation
University of Oxford
St Thomas' Hospital, London
British Heart Foundation
Diabetes UK
The University of Western Australia

Investigators

  • Principal Investigator: David B Dunger, Professor, University of Cambridge

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (ACTUAL)

April 1, 2017

Study Completion (ACTUAL)

June 1, 2017

Study Registration Dates

First Submitted

April 13, 2012

First Submitted That Met QC Criteria

April 19, 2012

First Posted (ESTIMATE)

April 20, 2012

Study Record Updates

Last Update Posted (ACTUAL)

June 28, 2018

Last Update Submitted That Met QC Criteria

June 26, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RP06
  • 2007-001039-72 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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