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

Ulcerative Colitis Clinical Trial

— Crocodex  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01171807
• Other study ID #: Crocodex
• Status: Recruiting
• Phase: Phase 2
• First received: July 28, 2010
• Last updated: June 27, 2011
• Start date: April 2003
• Est. completion date: December 2011

Study information

• Verified date: January 2003
• Source: Casa Sollievo della Sofferenza IRCCS
• Contact: Fabrizio Bossa, MD
• Phone: 00390882410235
• Email: f.bossa[@]operapadrepio.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Dexamethasone 21-phosphate
6 monthly infusions of dexamethasone 21-phosphate loaded into autologous erythrocytes

Locations

Country	Name	City	State
Italy	Casa Sollievo della Sofferenza Hospital	San Giovanni Rotondo

Sponsors (1)

Lead Sponsor	Collaborator
Casa Sollievo della Sofferenza IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No