Clinical trial NCT00382486: Low Dose Irradiation for Small Bowel Transplant
Official title: Low Dose Ex-Vivo X-Irradiation of the Allograft and Simultaneous Bone Marrow Cell Infusion to Enhance Intestinal/Multivisceral Allograft Survival
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Irreversible Intestinal Failure
Allograft Rejection
Keywords: Intestinal transplant
Bone marrow
Irradiation of allograft
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2006-09-29
Enrollment: 100
Sex: ALL
Minimum age (years): 17
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: The specific aims of this study is to improve short and long-term patient and graft survival, to reduce the incidence and severity of allograft rejection, to reduce the incidence of infection and to reduce and/or eventually eliminate the need for long-term immunosuppression.

Detailed description: The rationale behind this study involves the need to better manage rejection in the intestinal allograft recipient. Although tacrolimus based immunosuppression has made intestinal transplantation feasible, the requisite need for chronic high dose immunosuppression in order to control rejection has inhibited the wide spread clinical use and practicality of intestinal/multivisceral transplantation. The measures needed to prevent graft loss have frequently resulted in lethal infections, the leading cause of death. This trial is significant for determining if this new strategy of allograft immune-modulation with low dose ex-vivo irradiation and simultaneous done bone marrow cell infusion will favorably affect short and long term outcomes by reducing the risk of allograft rejection.

This trial is offered to all patients with irreversible intestinal failure who must undergo intestinal, combined liver-intestinal, and multivisceral transplantation at the University of Pittsburgh Medical Center. Patients are recruited through the referral system and no cold calling is carried out. Patient confidentiality is maintained by the use of codes to identify the study participants. All data is stored in a locked filing cabinets as a means to protect participants against a breach of confidentiality. This trial involves ex-vivo low dose irradiation of the intestinal allograft with or without adjunct donor bone marrow cell infusion. An intravenous bone marrow cell infusion is prepared form the thoracolumbar vertebral bodies harvested from cadaveric donors. Control subjects will be those who refuse to be enrolled in the study or those for whom donor bone marrow is not available. All patients will be treated perioperatively with thymoglobulin, a rabbit polyclonal anti-lymphocyte globulin at a dose of 5-10 mg/kg. Tacrolimus will be given in a standard fashion and from the outset as a single monotherapeutic agent to prevent early allograft rejection and promote graft acceptance. All patients will be monitored for rejection, graft function, opportunistic infections and GVHD. Surveillance endoscopy with guided mucosal biopsies will be obtained according to the standard protocol. Attention will be paid for any clinicopathologic changes suggestive of acute or chronic irradiation injuries.

The study closed for enrollment as of 9/30/03.

Eligibility criteria: Inclusion Criteria:

* all patients between 17 and 70 who are diagnosed with intestinal failure awaiting intestinal/multivisceral transplant

Exclusion Criteria:

* active systemic/abdominal infections
* incurable malignancy
* acquired immune deficiency syndrome
* severe cardiopulmonary insufficiency
* current alcoholism
* pregnant female

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Kareem M Abu-Elmagd, MD
role: PRINCIPAL_INVESTIGATOR
References: