Trial record 3 of 15 for:    Open Studies | "Facial Injuries"

Human Craniomaxillofacial Allotransplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Johns Hopkins University
Sponsor:
Information provided by (Responsible Party):
W. P. Andrew Lee, M.D., Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01889381
First received: June 26, 2013
Last updated: NA
Last verified: June 2013
History: No changes posted
  Purpose

Background: The human face is critically important for breathing, eating, seeing, and speaking/ communicating, but its most important job may be to look like a human face. Devastating facial deformities often cause affected individuals to avoid human contact and disappear from society. Although current surgical advancements can somewhat restore facial defects, this process often requires many operations and the resulting face only resembles the human face. To date, over 20 face transplants have been performed with highly encouraging functional and aesthetic results, but widespread clinical use has been limited due to the adverse effects of life-long and high-dose immunosuppression needed to prevent graft rejection. Risks include infection, cancer, and metabolic problems, all of which can greatly affect recipients' quality of life, make the procedure riskier, and jeopardize the potential benefits of face transplantation.

Study Design: This non-randomized, Phase II clinical trial will document the use of a new immunomodulatory protocol (aka - Pittsburgh Protocol, Starzl Protocol) for establishing face transplantation as a safe and effective reconstructive treatment for devastating injuries/ defects by minimizing maintenance immunosuppression therapy in face transplant patients. This protocol combines lymphocyte depletion with donor bone marrow cell infusion and has enabled graft survival using low doses of a single immunosuppressive drug followed by weaning of treatment. Initially designed for living-related solid organ donation, this regimen has been adapted for use with grafts donated by deceased donors. The investigators propose to perform 15 full or partial human face transplants employing this novel protocol.

Specific Aims: 1) To establish face transplantation as a safe and effective reconstructive strategy for the treatment of devastating facial injuries/defects; 2) To reduce the risk of rejection and enable allograft survival while minimizing the requirement for long-term, high-dose, multi-drug immunosuppression.

Significance of Research: Face transplantation could help injured individuals recover functionality, self-esteem, and the ability to reintegrate into family and social life as "whole" individuals. This protocol offers the potential for minimizing the morbidity of maintenance immunosuppression, thereby beneficially shifting the risk/benefit ratio of this life-enhancing procedure and enabling a wider clinical application of face transplantation.


Condition Intervention Phase
Facial Injuries
Traumatic Wounds and Injuries
Craniofacial Injuries
Craniofacial Defects
Drug: Bone marrow cell-based therapy & 1-drug immunosuppression.
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Human Craniomaxillofacial Allotransplantation

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Graft Survival [ Time Frame: Transplantation through end of study period (up to 5 years) ] [ Designated as safety issue: No ]
    Post-operative graft survival will be documented monthly Months 1-12 and quarterly (every 3 months) Years 2-5.


Secondary Outcome Measures:
  • Documentation of immunosuppression required by transplanted participants to maintain graft. [ Time Frame: Transplantation to end of study period (up to 5 years) ] [ Designated as safety issue: No ]
    Post-operative serum trough levels will be documented daily Days 1-28, semiweekly Weeks 5-12, weekly Weeks 13-25, biweekly Weeks 26-38, monthly Months 10-12, and quarterly (every 3 months) Years 2-5.


Estimated Enrollment: 15
Study Start Date: August 2012
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Transplantation)
Face transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning.
Drug: Bone marrow cell-based therapy & 1-drug immunosuppression.
This protocol uses a novel bone marrow cell-based therapy for composite tissue allotransplantation (CTA) rather than conventional triple-drug immunosuppression to facilitate long-term graft survival of deceased donor human faces under low-dose maintenance immunosuppression. Initial T-cell depletion with alemtuzumab is followed by upper extremity transplantation and tacrolimus maintenance therapy. Donor bone marrow cells are infused on Day 10 (±4 days) post-transplantation to elicit a host alloimmune response triggering exhaustion and deletion of the respective host (anti-donor) lymphocyte clones. Subsequently, tacrolimus therapy is given for at least 6 months before spaced weaning is considered in stable recipients.
Other Name: Deceased donor face transplantation

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recent (≥6 months) or remote (i.e., several decades) craniomaxillofacial injury
  • Male or female and of any race, color, or ethnicity.
  • Aged 18-60 years.
  • Strong desire to undergo craniomaxillofacial transplantation.
  • Completes the protocol informed consent form.
  • Non-smoker, defined by having never smoked or having quit >6 consecutive months prior to screening.
  • No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (see Exclusion Criteria below. If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of full or partial craniomaxillofacial transplantation.)
  • No co-existing psycho-social problems (i.e., alcoholism, drug abuse).
  • Negative for malignancy for past 5 years.
  • Negative for HIV at transplant.
  • Negative crossmatch with donor.
  • If female of child-bearing potential, negative serum pregnancy test.
  • If female of child-bearing potential, consent to use reliable contraception for at least one year following transplantation.
  • Consents to cell collection, storage, and bone marrow infusion as part of the treatment regime.
  • USA citizen or equivalent.
  • Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.

Exclusion Criteria:

  • Positive for any of the following conditions:

    • Untreated sepsis.
    • HIV (active or seropositive).
    • Active tuberculosis.
    • Active Hepatitis B infection.
    • Hepatitis C.
    • Viral encephalitis.
    • Toxoplasmosis.
    • Malignancy (within past 5 years).
    • Current/recent (within 3 months of donation/screening consent) IV drug abuse.
    • Paralysis of ischemic, traumatic, or congenital origin.
    • Infectious, post infectious, or inflammatory (axonal or demyelinating) neuropathy.
    • Toxic neuropathy (i.e. heavy metal poisoning, drug toxicity, industrial agent exposure).
    • Mixed connective tissue disease.
  • Conditions that, in the opinion of the study team, may impact the immunomodulatory protocol potentially exposing the recipient to an unacceptable risk under immunosuppressive treatment.
  • A history of medical non-compliance.
  • Sensitized recipients with high levels (50%) of panel-reactive HLA antibodies.
  • Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thallassemias, Sickle Cell disease, etc.
  • Mixed connective tissue diseases and collagen diseases can result in poor wound healing after surgery.
  • Conditions that may impact functional outcomes including Lipopolysaccharidosis and amyloidosis (may impact nerve regeneration) or rare disorders of bone healing like osteopetrosis.
  • Subjects with inadequate donor sites for autologous reconstruction in the event of post-transplant flap failure.
  • Patients considered unsuitable per the consulted Psychiatric/ Psychologic appraisal.
  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: NCT01889381

Locations
United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21287
Contact: Cynthia Cohen, DNP,RN,CRNP    410-502-3895    ccohen3@jhmi.edu   
Contact: Carisa M Cooney, MPH, CCRP    443-287-4629    ccooney3@jhmi.edu   
Principal Investigator: W. P. Andrew Lee, MD         
Sub-Investigator: Chad Gordon, DO         
Sub-Investigator: Patrick Byrne, MD         
Sub-Investigator: Gerald Brandacher, MD         
Sub-Investigator: Steven Bonawitz, MD         
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: W. P. Andrew Lee, MD Johns Hopkins University
  More Information

Additional Information:
Publications:
Responsible Party: W. P. Andrew Lee, M.D., Professor and Chairman, Department of Plastic and Reconstructive Surgery, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01889381     History of Changes
Other Study ID Numbers: NA_00067257
Study First Received: June 26, 2013
Last Updated: June 26, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Facial Injuries
Wounds and Injuries
Craniocerebral Trauma

ClinicalTrials.gov processed this record on August 28, 2014