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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01581476




Registration number
NCT01581476
Ethics application status
Date submitted
13/04/2012
Date registered
20/04/2012
Date last updated
28/06/2018

Titles & IDs
Public title
Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial
Scientific 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
Secondary ID [1] 0 0
2007-001039-72
Secondary ID [2] 0 0
RP06
Universal Trial Number (UTN)
Trial acronym
AdDIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Statin
Treatment: Drugs - ACE inhibitor
Treatment: Drugs - Placebo
Treatment: Drugs - Combination therapy

Active comparator: Statin - Participants receive active statin and placebo ACE Inhibitor

Active comparator: Angiotensin-converting enzyme inhibitor - Participants receive active ACE Inhibitor and placebo statin

Placebo comparator: Placebo - Participants receive placebo ACE Inhibitor and placebo statin

Other: Combination therapy - Participants receive both active ACE Inhibitor and active Statin


Treatment: Drugs: Statin
10mg daily for a minimum period of 2 years

Treatment: Drugs: 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.

Treatment: Drugs: Placebo
Participants receive statin placebo and ACEI placebo

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Albumin creatinine ratio
Timepoint [1] 0 0
2-4 years treatment duration
Secondary outcome [1] 0 0
Changes in CVD risk markers
Timepoint [1] 0 0
2-4 yrs treatment duration
Secondary outcome [2] 0 0
Changes in glomerular filtration rate (GFR)
Timepoint [2] 0 0
2-4 years treatment duration
Secondary outcome [3] 0 0
Retinopathy
Timepoint [3] 0 0
2-4 years treatment duration
Secondary outcome [4] 0 0
Quality of Life and Health Economics
Timepoint [4] 0 0
2-4 years treatment duration

Eligibility
Key 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.
Minimum age
10 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2017
Sample size
Target
Accrual to date
Final
443
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
University of Western Australia - Perth
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
University of Cambridge
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Juvenile Diabetes Research Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Diabetes UK
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
British Heart Foundation
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/industry
Name [4] 0 0
Pfizer
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
The University of Western Australia
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
The Hospital for Sick Children
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
University of Oxford
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
St Thomas' Hospital, London
Address [8] 0 0
Country [8] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01581476
Trial related presentations / publications
Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008 Mar 29;336(7646):697-701. doi: 10.1136/bmj.39478.378241.BE. Epub 2008 Mar 18.
Dunger DB, Schwarze CP, Cooper JD, Widmer B, Neil HA, Shield J, Edge JA, Jones TW, Daneman D, Dalton RN. Can we identify adolescents at high risk for nephropathy before the development of microalbuminuria? Diabet Med. 2007 Feb;24(2):131-6. doi: 10.1111/j.1464-5491.2006.02047.x.
Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group. Adolescent type 1 Diabetes Cardio-renal Intervention Trial (AdDIT). BMC Pediatr. 2009 Dec 17;9:79. doi: 10.1186/1471-2431-9-79.
Cherney DZ, Scholey JW, Daneman D, Dunger DB, Dalton RN, Moineddin R, Mahmud FH, Dekker R, Elia Y, Sochett E, Reich HN. Urinary markers of renal inflammation in adolescents with Type 1 diabetes mellitus and normoalbuminuria. Diabet Med. 2012 Oct;29(10):1297-302. doi: 10.1111/j.1464-5491.2012.03651.x.
Chiesa ST, Marcovecchio ML, Benitez-Aguirre P, Cameron FJ, Craig ME, Couper JJ, Davis EA, Dalton RN, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, Deanfield JE; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group. Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes. Hypertension. 2020 Dec;76(6):1734-1743. doi: 10.1161/HYPERTENSIONAHA.120.15721. Epub 2020 Oct 26.
Niechcial E, Acerini CL, Chiesa ST, Stevens T, Dalton RN, Daneman D, Deanfield JE, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, Marcovecchio ML; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group; Adolescent Type 1 Diabetes Cardio-renal Intervention Trial AdDIT Study Group. Medication Adherence During Adjunct Therapy With Statins and ACE Inhibitors in Adolescents With Type 1 Diabetes. Diabetes Care. 2020 May;43(5):1070-1076. doi: 10.2337/dc19-0884. Epub 2020 Feb 27.
Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB; AdDIT Study Group. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med. 2017 Nov 2;377(18):1733-1745. doi: 10.1056/NEJMoa1703518.
Har RL, Reich HN, Scholey JW, Daneman D, Dunger DB, Moineddin R, Dalton RN, Motran L, Elia Y, Deda L, Ostrovsky M, Sochett EB, Mahmud FH, Cherney DZ. The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes. PLoS One. 2014 Nov 13;9(11):e111131. doi: 10.1371/journal.pone.0111131. eCollection 2014.
Public notes

Contacts
Principal investigator
Name 0 0
David B Dunger, Professor
Address 0 0
University of Cambridge
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01581476