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Type 1 DiabetesPhase 3AdDITNCT01581476

Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial

A Phase 3 study testing Statin, ACE inhibitor and Combination therapy in people with Type 1 Diabetes, run by University of Cambridge at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 10 to 16 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Statin, ACE inhibitor and Combination therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
443 participants
Where
2 sitesin 2 countries
Study dates
Jan 2009to Jun 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Age 10 to 16 years.
  • T1D diagnosed for more than 1 year or C-peptide negative.
  • 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.

Who cannot join

  • Non T1D, i.e. type 2 diabetes, insulin dependent diabetes related to monogenic disease, secondary diabetes.
  • ACR based on six early morning urines deemed to be at low risk for subsequent development of CVD or DN.
  • Pregnancy or unwillingness to comply with contraceptive advice and regular pregnancy testing throughout the trial.
  • Breast feeding
  • Severe hyperlipidaemia and family history data to support diagnosis of familial hypercholesterolaemia.
  • Established hypertension unrelated to DN.
Show all 11Show fewer
  • Prior exposure to the investigational products, statins and ACEI.
  • Unwillingness/inability to comply with the study protocol.
  • Other co-morbidities considered unsuitable by the investigator (excluding treated hypothyroidism and coeliac disease).
  • Proliferative retinopathy.
  • Renal disease not associated with Type 1 Diabetes.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Australia1 site

  • University of Western Australia

    Perth

Other trials in Australia

Canada1 site

  • Hospital for Sick Children

    Toronto, Ontario

Other trials in Canada

About this study

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

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.

Read the 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.

Conditions
Type 1 Diabetes
Being tested
Statin, ACE inhibitor, Placebo, Combination therapy
Keywords
Adolescence
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • StatinDrug

    Also called Atorvastatin

    10mg daily for a minimum period of 2 years

  • ACE inhibitorDrug

    Also called Quinapril

    Starting dose of 5mg daily rising after 14 days to 10mg daily providing it is well tolerated for a minimum period of 2 years.

  • PlaceboDrug

    Participants receive statin placebo and ACEI placebo

  • Combination therapyDrug

    Also called Atorvastatin, Quinapril

    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.

Study groups in NCT01581476
Study groupRoleWhat they receive
StatinActive comparatorParticipants receive active statin and placebo ACE Inhibitor
Receives: Drug: Statin
Angiotensin-converting enzyme inhibitorActive comparatorParticipants receive active ACE Inhibitor and placebo statin
Receives: Drug: ACE inhibitor
PlaceboPlacebo comparatorParticipants receive placebo ACE Inhibitor and placebo statin
Receives: Drug: Placebo
Combination therapyOtherParticipants receive both active ACE Inhibitor and active Statin
Receives: Drug: Combination therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Albumin creatinine ratio

    The area under the curve over time of log ACR per year, with standardisation for gender, age and duration of disease

    Measured: 2-4 years treatment duration

Secondary outcomes (4)

  1. Changes in CVD risk markers

    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.

    Measured: 2-4 yrs treatment duration

  2. Changes in glomerular filtration rate (GFR)

    Changes in measures of GFR (plasma SDMA, creatinine adn cystatin C levels) assessed every 6 months during intervention period.

    Measured: 2-4 years treatment duration

  3. Retinopathy

    Changes in retinopathy scores and retinal microvascular structure (arteriolar or venular dilation, vascular fractile dimension, branching and tortuosity) assessed annually

    Measured: 2-4 years treatment duration

  4. Quality of Life and Health Economics

    Changes in quality of life measures and resource usage

    Measured: 2-4 years treatment duration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2012 (estimated)
  2. Study startJan 2009
  3. Primary completionApr 2017
  4. Study completionJun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Factorial
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
443 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01581476
Sponsor's protocol ID
RP06
Other IDs
2007-001039-72
Acronym
AdDIT
Status last verified
Jun 2018
First submitted
13 Apr 2012
Last updated
28 Jun 2018
Results posted
No
Data monitoring committee
Yes

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.

    PubMed 18349042

  • 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.

    PubMed 17257274

  • 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.

    PubMed 20017932

  • 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.

    PubMed 22416821

  • Clarke ABM, Curtis JR, Elia YT, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Clarson C, Couper JJ, Craig ME, Dalton RN, Davis EA, Marshall SM, Cherney DZI, Marcovecchio ML, Mahmud FH. Longitudinal evaluation of glomerular filtration rate across adolescence and early adulthood in youth with type 1 diabetes: associations with clinical and social risk factors. Front Endocrinol (Lausanne). 2026 Aug 26;17:1888628. doi: 10.3389/fendo.2026.1888628. eCollection 2026.

    PubMed 42718842

  • Prampolini B, Giton A, Frassineti S, Benitez-Aguirre P, Cameron FJ, Craig ME, Couper JJ, Dalton RN, Daneman D, Davis EA, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HA, Deanfield JE, Marcovecchio ML, Chiesa ST. Effect of statins and ACE inhibitors on the metabolome in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) cohort. Sci Rep. 2026 Apr 29. doi: 10.1038/s41598-026-50044-w. Online ahead of print.

    PubMed 42056188

  • Mahmud FH, Clarke ABM, Elia Y, Curtis J, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Clarson C, Couper JJ, Craig ME, Dalton RN, Daneman D, Davis EA, Deanfield JE, Donaghue KC, Jones TW, Marshall SM, Neil A, Marcovecchio ML. Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data. BMC Med. 2023 Dec 20;21(1):506. doi: 10.1186/s12916-023-03222-w.

    PubMed 38124088

  • 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.

    PubMed 33100044

  • 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.

    PubMed 32108022

  • 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.

    PubMed 29091568

  • 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.

    PubMed 25392936

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Statin, ACE inhibitor and Combination therapy in people with Type 1 Diabetes, run by University of Cambridge at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Albumin creatinine ratio (time frame: 2-4 years treatment duration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01581476, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2018.

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