ProtocolInternational Journal of Clinical Trials
Publication: Immunophenotype and genetic risk scores to improve autoantibody negative type 1 diabetes classification: study protocol
Int J Clin Trials. 2022;9(4):293-299.DOI10.18203/2349-3259.ijct20222690
Abstract
Background An estimated 10-30% of type 1 diabetes (T1D) individuals do not have detectable autoantibodies at diagnosis, thus are classified as “idiopathic” or “non-immune.” Given the non-pathogenic role of islet autoantibodies, the validity of excluding an immune basis for disease in such individuals needs to be questioned. The pan-autoantibody negative type 1 diabetes in adults (PANDA) study aims to characterise the immune, clinical and metabolic phenotype of autoantibody negative T1D individuals.
Methods This is a two-part, multi-centre study which is recruiting 100 participants: autoantibody positive T1D (N=25), autoantibody negative T1D (N=25), latent autoimmune diabetes in adults (N=25) and age- and sex-matched normoglycaemic control (N=25) individuals. Study 1 involves baseline pathology collection and high dimensional immune-phenotyping using flow cytometry. DNA will be extracted from saliva samples to calculate type 1 diabetes genetic risk scores (T1DGRS). Autoantibody negative individuals will undergo monogenic diabetes testing. Study 2 is a prospective, longitudinal sub-study of study 1 participants within 5 years of diagnosis. Beta cell function will be assessed using glucagon stimulated C-peptide at 0, 9 and 18 months. The primary outcome of study 1 is to determine the phenotype of immune cells in autoantibody positive and negative T1D compared to healthy controls. Secondary outcomes of study 1 include clinical and metabolic characteristics and the T1DGRS. The primary outcome of study 2 is the rate of decline of stimulated C-peptide over time.
Conclusions The PANDA study is the first study of its kind which aims to improve diagnosis and characterisation of autoantibody negative T1D.
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Affiliations
- Department of Diabetes and Metabolism, UNSW Sydney, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia
- Human Immune Disorders, Garvan Institute of Medical Research, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia
- Charles Perkins Centre, Sydney Medical School, NSW, Australia The Children’s Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Australia
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
- Pacific Northwest Research Institute, Seattle, Washington, USA
- Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, Australia
- 1Department of Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia