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

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ClinicalTrials.gov Identifier: NCT01581476
Recruitment Status : Completed
First Posted : April 20, 2012
Last Update Posted : June 28, 2018
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
David Dunger, 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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Statin Drug: ACE inhibitor Drug: Placebo Drug: Combination therapy 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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 443 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : January 2009
Actual Primary Completion Date : April 2017
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Quinapril

Placebo Comparator: Placebo
Participants receive placebo ACE Inhibitor and placebo statin
Drug: Placebo
Participants receive statin placebo and ACEI placebo

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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. 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.

  3. 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

  4. Quality of Life and Health Economics [ Time Frame: 2-4 years treatment duration ]
    Changes in quality of life measures and resource usage



Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01581476


Locations
Australia
University of Western Australia
Perth, Australia
Canada, Ontario
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

Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Dunger, Professor David Dunger, University of Cambridge
ClinicalTrials.gov Identifier: NCT01581476     History of Changes
Other Study ID Numbers: RP06
2007-001039-72 ( EudraCT Number )
First Posted: April 20, 2012    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018

Keywords provided by David Dunger, University of Cambridge:
Adolescence

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Atorvastatin Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Quinapril
Angiotensin-Converting Enzyme Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Protease Inhibitors
Antihypertensive Agents