Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of erythrocyte-mediated delivery of dexamethasone in steroid-dependent ulcerative colitis patients

Detailed Description
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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.

Official Title
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PHASE 2 STUDY OF DEXAMETHASONE 21-PHOSPHATE LOADED INTO AUTOLOGOUS ERYTHROCYTES IN STEROID-DEPENDENT ULCERATIVE COLITIS PATIENTS

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Dexamethasone 21-phosphate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexamethasone 21-phosphate encapsulated into red cells<br> | Drug: Dexamethasone 21-phosphate<br>* 6 monthly infusions of dexamethasone 21-phosphate loaded into autologous erythrocytes<br>|
| Sham Comparator: Placebo<br> | Drug: Dexamethasone 21-phosphate<br>* 6 monthly infusions of dexamethasone 21-phosphate loaded into autologous erythrocytes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients able to discontinue oral corticosteroids while maintaining clinical remission or stable condition | Patients in clinical remission or mild activity on oral corticosteroids will be treated with 6 monthly infusion of Dexamethasone 21-phosphate loaded into autologous erythrocytes. During the treatment period, oral corticosteroids will be gradually discontinued. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with disappearance of steroid-related events | Patients will be evaluated by means of standard questionnaire to investigate the steroid-related adverse events at study entry and during the treatment period. | 6 months | 
| The modification of biochemical and endoscopic parameters | All patients underwent to a complete biochemical and endoscopic evaluation before the randomization and at the end of the study. | 6 months | 
| The pharmacokinetics of Dex 21-P loaded into red blood cells | Plasma concentrations of free dexamethasone will be measured immediately at end of each infusion and after 1, 15, and 30 days. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative colitis, Steroid-dependency, Steroid adverse events, Erythrocytes