REPLACE is a randomized controlled trial and is part of the Double Edge, a large research group with professors, post docs and PhD students from Odense University Hospital, Rigshospitalet, and Aarhus University Hospital, with Primary Investigator Professor Jens Otto Lunde Jørgensen. REPLACE originates from Odense University Hospital and Professor Marianne Skovsager Andersen is sponsor of the study.
The primary aim of REPLACE is to generate evidence-based guidance for management of GIA in patients using patient reported outcomes as a key tool for inclusion and outcome.
Glucocorticoid-induced adrenal insufficiency (GIA) may occur after termination of long-term glucocorticoid (GC) treatment. GIA is usually diagnosed by a short-synacthen-test (SST), and the standard treatment is hydrocortisone replacement.
After prednisolone cessation in polymyalgia rheumatic (PMR) and giant cell arteritis (GCA) patients, GIA prevalence was 1.6%, however 33% reported GIA symptoms (scores ≤85) according to the Addison’s disease-specific quality-of-life questionnaire (AddiQoL-30). Cortisol response to the SST may not validly assess normalisation of the diurnal hypothalamic-pituitary-adrenal (HPA)-axis.
REPLACE is a multi-centre randomized, double-blinded placebo-controlled study – and the first RCT to randomize patients with low AddiQoL-30 score after long-term GC use to hydrocortisone treatment or placebo. Eligible participants have PMR and/or GCA and are in GC free remission for 2-12 weeks after long-term prednisolone treatment (>12 weeks). Participants will be assigned to one of the study groups according to their symptom-score (AddiQoL-30) and the result of the SST:
RCT-group:
AddiQoL-score <85 or 30 min. cortisol level >100 nmol/L and <420 nmol/L
n=100
Control-group 1:
AddiQoL-score >85 and 30 min. cortisol level >420 nmol/L
n=150
Control-group 2:
30 min. cortisol level <100 nmol/L regardless of AddiQoL-score
n=20
All groups will participate in a standardized baseline visit. The RCT-group is randomized to either hydrocortisone or placebo for 16 weeks with repetition of baseline investigations at end of study.
Collaborating researchers and departments:
Department of Endocrinology, Odense University Hospital:
- Sponsor, Professor Marianne Skovsager Andersen, MD, PhD, DmSci
- PhD-student Hajir Al-Jorani, MD
- PhD-student Anja Fenger Dreyer, MD
- Post doc Richard Christian Jensen, MD, PhD
- Associate Professor Dorte Glintborg, MD, PhD, DmSci
- Associate Professor Louise Lehmann Christensen, MD, PhD
Department of Endocrinology and Internal Medicine, Aarhus University Hospital:
- Professor Jens Otto Lunde Jørgensen, MD, DmSci
Department of Endocrinology and Metabolism, Rigshospitalet:
- Professor Ulla Feldt-Rasmussen, MD, DmSci
Department of Rheumatology, Svendborg Hospital:
- Associate Professor Søren Andreas Just, MD, PhD
Department of Rheumatology, Odense University Hospital:
- Anne Voss, MD, PhD
Funding
The REPLACE study is funded by the Novo Nordisk Foundation as part of a collaborative grant entitled "DOUBLE EDGE – Characterization and mitigation of adverse effects of glucocorticoid treatment" (NNF20OC0063280).
PhD-student Anja Fenger Dreyer has received a 1-yearPhD stipend from the Region of Southern Denmark.
PhD-student Anja Fenger Dreyer has received a travel grant from the Danish Society of Endocrinology.