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

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

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

Study Overview

• Status: Unknown
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Dexamethasone 21-phosphate

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fabrizio Bossa, MD; Phone Number: 00390882410235; Email: f.bossa@operapadrepio.it
• Study Contact Backup: Name: Angelo Andriulli, MD; Phone Number: 00390882410263; Email: a.andriulli@operapadrepio.it

Study Locations

• Italy
  • San Giovanni Rotondo, Italy, 71013
    • Recruiting
    • Casa Sollievo della Sofferenza Hospital
    • Contact: Fabrizio Bossa, MD; Phone Number: 00390882410235; Email: f.bossa@operapadrepio.it
    • Contact: Angelo Andriulli, MD; Phone Number: 00390882410263; Email: a.andriulli@operapadrepio.it
    • Sub-Investigator: Fabrizio Bossa, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Casa Sollievo della Sofferenza IRCCS
• Investigators: Principal Investigator: Angelo Andriulli, MD, Casa Sollievo della Sofferenza Hospital

Publications and helpful links

General Publications

• Bossa F, Annese V, Valvano MR, Latiano A, Martino G, Rossi L, Magnani M, Palmieri O, Serafini S, Damonte G, De Santo E, Andriulli A. Erythrocytes-mediated delivery of dexamethasone 21-phosphate in steroid-dependent ulcerative colitis: a randomized, double-blind Sham-controlled study. Inflamm Bowel Dis. 2013 Aug;19(9):1872-9. doi: 10.1097/MIB.0b013e3182874065.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Anticipated): June 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (Estimate): July 29, 2010

Study Record Updates

• Last Update Posted (Estimate): June 28, 2011
• Last Update Submitted That Met QC Criteria: June 27, 2011
• Last Verified: January 1, 2003

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Erythrocytes; Steroid-dependency; Steroid adverse events
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Dexamethasone 21-phosphate
• Other Study ID Numbers: Crocodex