Title
Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis
PHASE 2 STUDY OF DEXAMETHASONE 21-PHOSPHATE LOADED INTO AUTOLOGOUS ERYTHROCYTES IN STEROID-DEPENDENT ULCERATIVE COLITIS PATIENTS
Phase
Phase 2Lead Sponsor
Casa Sollievo della Sofferenza IRCCSStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Ulcerative ColitisIntervention/Treatment
urea ...Study Participants
40The purpose of this study is to investigate the efficacy and safety of erythrocyte-mediated delivery of dexamethasone in steroid-dependent ulcerative colitis patients
Medical treatment of patients with ulcerative colitis (UC) presents a constant challenge. Corticosteroids are effective in the majority of patients, but benefits are offset by adverse events. For steroid-dependent patients therapeutic choices are limited to azathioprine/6-mercaptopurine, methotrexate and infliximab; however, 25% of more patients do not respond, become intolerant, or have contraindications (e.g. history of neoplasia) to these drugs.
A novel method of corticosteroids delivery by loading dexamethasone 21-phosphate into red blood cells has been validated. Owing to their long life span in the circulation and the capability of their cellular membrane to be opened and resealed in appropriate conditions, erythrocytes are excellent drug carriers. An ideal drug to be encapsulated into erythrocytes is Dex 21-P, a biologically inactive compound which undergoes dephosphorylation by intra-erythrocyte enzymes releasing the active metabolite, dexamethasone, by simple passive diffusion through cell membranes. In a previous pilot study in a cohort of steroid-dependent patients with inactive inflammatory bowel disease, Dexamethasone 21-phosphate loaded into autologous erythrocytes allowed to complete withdrawal of systemic steroids, and the overall cumulative exposure to corticosteroids from Dex 21-P-encapsulated erythrocytes (about 5-10 mg per month) was far less than conventional corticosteroids, and this translated into a lower rate of steroid-related events.
Inclusion Criteria: adult patients steroid-dependent ulcerative colitis clinical remission or mild clinical activity Exclusion Criteria: uncontrolled diabetes severe comorbidities (renal failure, heart failure, cirrhosis, neoplasia) previous exposure to biologic therapy pregnancy of breast feeding alcohol or drug abuse mental illness