Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial

Type 1 Diabetes Clinical Trial

— AdDIT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01581476
• Other study ID #: RP06
• Secondary ID: 2007-001039-72
• Status: Completed
• Phase: Phase 3
• Start date: January 2009
• Est. completion date: June 2017

Study information

• Verified date: June 2018
• Source: University of Cambridge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 443
• Est. completion date: June 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Statin
10mg daily for a minimum period of 2 years
• 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.
• Placebo
Participants receive statin placebo and ACEI placebo
• 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.

Locations

Country	Name	City	State
Australia	University of Western Australia	Perth
Canada	Hospital for Sick Children	Toronto	Ontario

Sponsors (9)

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

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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):12 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes in CVD risk markers	Changes in measures of: cIMT, FMD, EndoPAT and PWV between baseline and the end of intervention period; 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
Secondary	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.	2-4 years treatment duration
Secondary	Retinopathy	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
Secondary	Quality of Life and Health Economics	Changes in quality of life measures and resource usage	2-4 years treatment duration

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