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

Tracking of Risk for diabetic nephropathy and cardiovascular disease in young people with type 1 diabetes recruited to the AdDIT Study
Status – active

AdDIT was the first randomised controlled trial assessing the effects of ACE inhibitors and statins in in a rarely studied population of adolescents with T1D at high risk for complications.

The AdDIT trial showed both ACE inhibitor and statin therapy were well tolerated and the overall drug adherence was 75%.

Treatment with ACE inhibitor or statin did not have any significant effect on the primary outcome, area under the curve of albumin creatinine ratio(ACR).  However, the study showed that treatment with ACE inhibitor was associated with a 43% decrease in the incidence of microalbuminuria, which although of marginal statistical significance, may be of clinical importance. Even if ACE inhibitors reduce only sporadic increases in ACR leading to transient or intermittent cases of microalbuminuria, this could result in a long term beneficial effect in terms of hard end points, such as nephropathy and cardiovascular disease,

Statins resulted in reductions in lipid levels and hsCRP, but there was no effect on cIMT.

A delayed ‘legacy effect’ of early treatment with ACE inhibitors or statins could still occur, where reduced vascular complications emerged beyond the duration of the original trials.

The AdDIT cohort are now in follow-up to evaluate the potential benefits of early intervention with ACE inhibitors and statins. This is a longitudinal observational study of all participants completing the AdDIT trial both from the Interventional and Observational groups, up to 5 years.

The follow-up of the AdDIT cohort is based on similar measures to those used in the original trial and consists of a final assessment which will take place 5 years after participants completed the AdDIT Trial. This follow up visit will be identical to the AdDIT baseline & 12 month assessments and include data/sample collection and  cardiovascular, retinopathy and neuropathy assessments.

 

Key publications

•          Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group. Adolescent type 1 Diabetes Cardio-renal Intervention Trial (AdDIT). BMC Pediatric 2009; 9:17. [all AdDIT Investigators acknowledged and appear under the Collaborators link in PubMed)

•          Marcovecchio ML, Woodside J, Jones T, Daneman D, Neil A, Prevost T, Dalton RN, Deanfield J, Dunger DB; AdDIT Investigators. Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT): urinary screening and baseline biochemical and cardiovascular assessments. Diabetes Care. 2014; 37:805-13. [all AdDIT Investigators acknowledged and appear under the Collaborators link in PubMed)

•          Maftei O, Pena AS, Sullivan T, Jones TW, Donaghue KC, Cameron FJ, Davis E, Cotterill A, Craig ME, Gent R, Dalton N, Daneman D, Dunger D, Deanfield J, Couper JJ; AdDIT Study Group. Early atherosclerosis relates to urinary albumin excretion and cardiovascular risk factors in adolescents with type 1 diabetes: Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT). Diabetes Care. 2014; 37:3069-75. [no AdDIT collaborators link included]

•          Cho YH, Craig ME, Davis EA, Cotterill AM, Couper JJ, Cameron FJ, Benitez-Aguirre PZ, Dalton RN, Dunger DB, Jones TW, Donaghue KC; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (Adolescent Type 1 Diabetes cardio-renal interventional trial). Diabetes Care 2015; 38:676-81. [AdDIT investigators acknowledged and will appear under the Collaborators link in PubMed)

•          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;377(18):1733-1745.

•          Marcovecchio ML, Chiesa ST, Armitage J, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group. Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Diabetes Care 2018;41(9):1963-1969

•          Marcovecchio ML, Dalton RN, Daneman D, Deanfield J, Jones TW, Neil HAW, Dunger DB, on behalf of the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) study group. A new strategy for vascular complications in young people with type 1 diabetes mellitus.  Nat Rev Endocrinol. 2019 Jul;15(7):429-435

•          Benitez-Aguirre PZ, Wong TY, Craig ME, Davis EA, Cotterill A, Couper JJ, Cameron FJ, Mahmud FH, Jones TW, Hodgson LAB, Dalton RN, Dunger DB, Donaghue KC; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes. Diabetologia. 2018 Apr;61(4):968-976.

•          Niechciał E, Acerini CL, Chiesa S, Stevens T, Dalton RN, Daneman D, Deanfield J, Jones TW, MD; Mahmud FH, Marshall SM, Neil HAW, Dunger DB, Marcovecchio ML; on behalf of the 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.

•         Marcovecchio ML, Colombo M, Dalton RN, McKeigue PM, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Couper JJ, Craig ME, Daneman D, Davis EA, Deanfield JE, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil A, Colhoun HM, Dunger DB; AdDIT and the SDRNT1BIO Investigators. Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes. Pediatric Diabeets 020 Aug 11. doi: 10.1111/pedi.13095. Online ahead of print.

•          Chiesa ST, Marcovecchio MLBenitez-Aguirre P, Craig M, Couper J, Davis E, Dalton RN, Daneman D, Donaghue K, Jones T, Mahmud FH, Marshall S, Neil HAW, Dunger D, Deanfield J. Vascular effects of ACE inhibitors and statins in adolescents with type 1 diabetes: the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT). Hypertension 2020 Dec;76(6):1734-1743