Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial

NCT01581476 | Completed Phase 3 DMC

• 2 other identifiers: RP062007-001039-72
• Study Type: interventional
• Target: 443
• Locations: 2 countries
• Sites: 2

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.

Conditions

Type 1 Diabetes

Keywords

Adolescence

Outcome Measures

Primary Outcomes (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

  2-4 years treatment duration

Secondary Outcomes (4)

• Changes in CVD risk markers

  2-4 yrs treatment duration

• Changes in glomerular filtration rate (GFR)

  2-4 years treatment duration

• Retinopathy

  2-4 years treatment duration

• Quality of Life and Health Economics

  2-4 years treatment duration

Study Arms (4)

Statin

ACTIVE COMPARATOR

Participants receive active statin and placebo ACE Inhibitor

Drug: Statin

Angiotensin-converting enzyme inhibitor

ACTIVE COMPARATOR

Participants receive active ACE Inhibitor and placebo statin

Drug: ACE inhibitor

Placebo

PLACEBO COMPARATOR

Participants receive placebo ACE Inhibitor and placebo statin

Drug: Placebo

Combination therapy

OTHER

Participants receive both active ACE Inhibitor and active Statin

Drug: Combination therapy

Interventions

Statin DRUG

10mg daily for a minimum period of 2 years

Also known as: Atorvastatin

Statin

ACE inhibitor DRUG

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

Also known as: Quinapril

Angiotensin-converting enzyme inhibitor

Placebo DRUG

Participants receive statin placebo and ACEI placebo

Placebo

Combination therapy DRUG

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.

Also known as: Atorvastatin, Quinapril

Combination therapy

Eligibility Criteria

• Age: 10 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

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

Study Sites (2)

University of Western Australia

Perth, Australia

Location

Hospital for Sick Children

Toronto, Ontario, Canada

Location

Related Publications (9)

• 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.

  PMID: 18349042 BACKGROUND

• 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.

  PMID: 17257274 BACKGROUND

• 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.

  PMID: 20017932 BACKGROUND

• 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.

  PMID: 22416821 RESULT

• 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.

  PMID: 38124088 DERIVED

• 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.

  PMID: 33100044 DERIVED

• 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.

  PMID: 32108022 DERIVED

• 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.

  PMID: 29091568 DERIVED

• 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.

  PMID: 25392936 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Angiotensin-Converting Enzyme Inhibitors; Quinapril; Combined Modality Therapy

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Protease Inhibitors; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics

Study Officials

• David B Dunger, Professor

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor David Dunger

Study Record Dates

• First Submitted: April 13, 2012
• First Posted: April 20, 2012
• Study Start: January 1, 2009
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 28, 2018

Record last verified: 2018-06

Locations

AU (1); CA (1)