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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2003 by Casa Sollievo della Sofferenza IRCCS.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Casa Sollievo della Sofferenza IRCCS
ClinicalTrials.gov Identifier:
NCT01171807
First received: July 28, 2010
Last updated: June 27, 2011
Last verified: January 2003
  Purpose

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


Condition Intervention Phase
Ulcerative Colitis
Drug: Dexamethasone 21-phosphate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: PHASE 2 STUDY OF DEXAMETHASONE 21-PHOSPHATE LOADED INTO AUTOLOGOUS ERYTHROCYTES IN STEROID-DEPENDENT ULCERATIVE COLITIS PATIENTS

Resource links provided by NLM:


Further study details as provided by Casa Sollievo della Sofferenza IRCCS:

Primary Outcome Measures:
  • The proportion of patients able to discontinue oral corticosteroids while maintaining clinical remission or stable condition [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • The proportion of patients with disappearance of steroid-related events [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Patients will be evaluated by means of standard questionnaire to investigate the steroid-related adverse events at study entry and during the treatment period.

  • The modification of biochemical and endoscopic parameters [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    All patients underwent to a complete biochemical and endoscopic evaluation before the randomization and at the end of the study.

  • The pharmacokinetics of Dex 21-P loaded into red blood cells [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Plasma concentrations of free dexamethasone will be measured immediately at end of each infusion and after 1, 15, and 30 days.


Estimated Enrollment: 40
Study Start Date: April 2003
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dexamethasone 21-phosphate encapsulated into red cells Drug: Dexamethasone 21-phosphate
6 monthly infusions of dexamethasone 21-phosphate loaded into autologous erythrocytes
Sham Comparator: Placebo Drug: Dexamethasone 21-phosphate
6 monthly infusions of dexamethasone 21-phosphate loaded into autologous erythrocytes

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01171807

Contacts
Contact: Fabrizio Bossa, MD 00390882410235 f.bossa@operapadrepio.it
Contact: Angelo Andriulli, MD 00390882410263 a.andriulli@operapadrepio.it

Locations
Italy
Casa Sollievo della Sofferenza Hospital Recruiting
San Giovanni Rotondo, Italy, 71013
Contact: Fabrizio Bossa, MD    00390882410235    f.bossa@operapadrepio.it   
Contact: Angelo Andriulli, MD    00390882410263    a.andriulli@operapadrepio.it   
Sub-Investigator: Fabrizio Bossa, MD         
Sponsors and Collaborators
Casa Sollievo della Sofferenza IRCCS
Investigators
Principal Investigator: Angelo Andriulli, MD Casa Sollievo della Sofferenza Hospital
  More Information

No publications provided by Casa Sollievo della Sofferenza IRCCS

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fabrizio Bossa, Casa Sollievo della Sofferenza Hospital
ClinicalTrials.gov Identifier: NCT01171807     History of Changes
Other Study ID Numbers: Crocodex
Study First Received: July 28, 2010
Last Updated: June 27, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by Casa Sollievo della Sofferenza IRCCS:
Ulcerative colitis
Steroid-dependency
Steroid adverse events
Erythrocytes

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014