Facial Vascularized Composite Allotransplantation, Functional Recovery
Conditions
Keywords
Vascularized composite allotransplantation, Face transplantation, Composite tissue allotransplantation, Rehabilitation
Brief summary
The primary objective of this study is to evaluate the 5-year (60-month) allograft survival rate of facial vascularized composite allotransplantation performed under the standardized CONSORT clinical protocol.
Detailed description
The study population includes adults (18+) with severe facial disfigurement meeting the following criteria: * Anatomic Severity: Loss of total facial surface area or absence of a critical central unit (e.g., nose or lips). * Refractory Status: Defects not reconstructible via conventional autologous surgical techniques. * Impairment: Significant deficits in essential functions (speech, swallowing, breathing, eyelid closure).
Interventions
PROCEDUREFacial Vascularized Composite Allotransplantation (VCA)
Facial VCA, performed to treat severe facial defects. This procedure will be performed by qualified surgeons in accordance with standard institutional surgical practices.
Sponsors
Yale University
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A total of five procedures will be performed. Given the five-procedure cap, enrollment opportunities will be limited and dependent upon donor availability, candidate eligibility, multidisciplinary review, and regulatory readiness across participating sites.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants: * Competent to provide informed consent, as determined through structured clinical assessment by qualified study personnel, and able to demonstrate adequate psychosocial support, including caregiver or other support-person assistance as needed, to facilitate postoperative recovery, adherence to immunosuppressive therapy, and long-term study follow-up. * Non smoker at the time of transplantation (no cigarettes, vaping, or nicotine products), with counseling and support offered for cessation as needed. * For participants of reproductive potential: * Negative pregnancy test at listing and again immediately prior to transplant. * Agreement to use effective contraception throughout study participation and for at least 12 months post transplant. * A serum pregnancy test performed shortly before transplantation will be determinative; individuals who are pregnant at that time will be screen failures for the transplant intervention, though may be offered continued follow up and support as appropriate. * Willingness to undergo comprehensive psychosocial evaluation and ongoing monitoring by the multidisciplinary team. * Demonstrated motivation for transplantation and understanding of the investigational nature of facial VCA, including its risks, potential benefits, alternatives, and long-term commitments. * Evidence of psychological stability and adaptive coping, with attention to prior trauma, grief, and body-image disturbances; stable treatment for conditions such as depression, anxiety, or post-traumatic stress disorder is acceptable when documented and appropriately managed. * Demonstrated capacity for adherence and, when available, a history of adherence to complex medical regimens, such as chronic disease treatment, dialysis, or transplant care, recognizing that prior barriers may be mitigated through structured supports and longitudinal follow-up. * Availability of adequate family, caregiver, and/or social support, including an identified caregiver, support person, or formal support services, sufficient to assist with postoperative recovery, medication adherence, transportation, and psychosocial needs. A caregiver/family information sheet will be provided to support persons to promote realistic expectations prior to consent. * Final psychosocial approval by a transplant mental health professional in consultation with the broader psychosocial team. * Severe facial disfigurement involving one or more central facial structures or functional subunits (e.g., perioral, periorbital, nasal, midface) with major impact on function and appearance. * Disfigurement must result in substantial functional impairment (e.g., speech, mastication, swallowing, breathing, eyelid closure, eye protection) and/or psychosocial burden (e.g., profound body image disturbance, social withdrawal, stigma) such that conventional reconstructive options are exhausted, infeasible, or reasonably expected to be inadequate for restoring function or appearance. * No active malignancy. * Prior non viral, non melanoma malignancy may be eligible if in complete remission for at least 5 years and deemed acceptable risk for immunosuppression by oncology and the transplant team. * No decompensated or advanced cirrhosis. Individuals with compensated cirrhosis or chronic liver disease may be considered following hepatology evaluation and documented clearance. * No uncontrolled medical comorbidities that would pose an unacceptable surgical or immunosuppressive risk (e.g., uncontrolled diabetes with end organ damage, uncontrolled hypertension, uncorrected coagulopathy). * Overall medical status compatible with major surgery and lifelong immunosuppression, with willingness to comply with intensive early follow up and ongoing protocol requirements. * Identified plan for access to immunosuppressive medications and required follow up care (e.g., insurance coverage, assistance programs, institutional support), coordinated with social work and financial counseling. * Willingness and ability, with available supports, to attend required follow up visits (in person or via approved telehealth where appropriate). Donor: * Legal declaration of brain death * Documented consent for VCA donation. * ABO and HLA compatibility with the intended recipient. * Negative crossmatch with the intended recipient (unless protocol specified exceptions are approved by immunology and the IRB). * EBV and CMV serostatus known (CMV mismatch (donor-positive/recipient-negative (D+/R-) is not automatically exclusionary but managed by the multidisciplinary study team). * Facial anatomy suitable for transplant (no significant facial trauma, major congenital anomalies, or prior facial surgery that would preclude safe procurement or acceptable aesthetic/functional outcomes). * Reasonably matched skin tone and sex, where feasible, to support psychosocial and aesthetic integration.
Exclusion criteria
* Anatomical or surgical factors that render transplantation unsafe or technically unfeasible (e.g., prohibitive vascular disease, prior surgeries precluding adequate anastomoses) in the judgment of the surgical team. * Positive Human Immunodeficiency Virus (HIV) serology (unless future evidence and institutional policy support inclusion under tightly controlled conditions). * Active or inadequately treated serious infection, including tuberculosis, hepatitis B or C with uncontrolled viremia, or syphilis. * Active malignancy. * History of melanoma or other high risk, virus driven malignancies. * Malignancy in remission \<5 years, except for selected low risk, non viral cancers explicitly reviewed and approved by the transplant team. * Must have clearance for transplant from oncology. * Decompensated liver disease without hepatology clearance * Decompensated or advanced cirrhosis * Uncontrolled or uncorrectable comorbidities that substantially elevate perioperative or immunosuppressive risk despite optimization efforts (e.g., uncontrolled diabetes with end organ damage, uncontrolled hypertension, uncorrected coagulopathy). * Current pregnancy or stated intent to become pregnant within 12 months of transplant. * Inability or unwillingness to use effective contraception, when applicable. * Documented pattern of poor adherence or inability to engage with follow up despite reasonable, trauma informed efforts to reduce barriers (e.g., transportation, scheduling, health literacy, financial support). * Active psychiatric illness that currently impairs judgment, decisional capacity, or capacity to adhere to care (e.g., untreated psychosis, severe untreated depression with suicidality, impaired reality testing), as determined by the transplant psychosocial team. * Smoking at the time of transplantation (including cigarettes, vaping, or nicotine products) * Active substance use disorder (alcohol or drugs) without sustained remission and without adequate recovery supports, unless the multidisciplinary team determines that risk has been sufficiently mitigated. * Persistent, unrealistic expectations about transplant outcomes that do not resolve despite structured education and counseling. * Absence of any viable psychosocial or financial support pathway after reasonable efforts to develop one (e.g., no caregiver and no alternative formal support options, or no feasible mechanism to obtain essential medications). * Inability to provide informed consent, even with appropriate accommodations (e.g., language services, plain language materials, decision aids), and no appropriate legally authorized representative where required. * Any other condition or circumstance judged by the multidisciplinary transplant team and IRB to pose unacceptable risk or compromise ethical conduct of the study. Donor: * Positive serology for HIV, HBV, HCV, TB, or syphilis, or other identified transmissible infections per current OPTN/UNOS and PHS guidance. HTLV testing will be conducted in line with current OPTN standards for donors with potential transmissible infections that are treatable in the recipient. HCV NAT+ donors may be considered with planned treatment of disease transmission and informed consent. HBcAb+ donors are acceptable with post-transplant prophylaxis. * Known history of cancer, especially head/neck or hematologic malignancy. * Remote history of low grade or in situ malignancies may be considered if location was not in the anticipated or adjacent donor tissue and appropriate disease free survival prior to donation (e.g. remote basal cell carcinoma on the trunk for a face VCA donor, or cheek BCC in a hand donor). * Permanent facial tattoos or highly identifiable markings judged incompatible with the recipient's preferences or the clinical/ethical judgment of the transplant team. * History of head/neck radiation that compromises tissue viability. * Public Health Service (PHS) increased risk donors (e.g., recent IV drug use, incarceration) will not be automatically excluded but will require case by case risk assessment, full disclosure to the recipient, and documented multidisciplinary approval.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Allograft Survival at 60 months | Day 0 (surgery), weekly during initial hospitalization, months 1, 3, 6, 12, 18, 24, and annually thereafter through Month 60 | Allograft survival is defined as the continued presence of the transplanted facial tissue with evidence of adequate vascular perfusion assessed as clinical evaluation by the surgical team. Survival is a binary categorical variable (Success/Failure). Failure is defined as total graft loss necessitating surgical removal (explantation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Motor Function Change | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Number of participants with improvement in motor function change. Assessed using a clinical grading in mild, moderate, severe for every facial muscle. |
| Number of participants with Sensory Restoration | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Number of participants with Sensory Restoration. Quantified by Static Two-Point Discrimination (2PD) measured in millimeters (mm) across the V2 (maxillary) and V3 (mandibular) distributions. A decrease in the minimum distance perceived as two distinct points indicates nerve regeneration and improved tactile acuity. |
| Mean score General Health Status (PROMIS-29 v2.0) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | 29-item questionnaire that measures general physical, mental, and social health-related quality of life. Results are converted into T-scores where 50 is the average for the U.S. general population, with a standard deviation of 10. Higher score means worse symptoms or better ability. |
| Mean score Health Utility (EQ-5D-5L) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life. It consists of consists of 5 dimensions each scored: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions. |
| Mean score Face-Specific PROMs (FACE-Q) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | The FACE-Q is a validated patient-reported outcome measure (PROM) used to evaluate appearance, health-related quality of life, and satisfaction among patients undergoing facial aesthetic, plastic, or reconstructive procedures. Scores ranging from 0 to 100, where higher numbers mean better satisfaction or quality of life. |
| Number of participants with Opportunistic infections | Day 0 (surgery) through Month 60 | Number of participants with Opportunistic infections |
| Number of participants with Malignancies | Day 0 (surgery) through Month 60 | Number of participants with Malignancies |
| Number of participants with Organ toxicity | Day 0 (surgery) through Month 60 | Number of participants with Organ toxicity |
| Number of participants that complete all assessments | Day 0 (surgery) through Month 60 | Number of participants that complete all assessments |
| Number of participants that complete the Central Review Agreement | Day 0 (surgery) through Month 60 | Number of participants that complete the Central Review Agreement |
| Acute Rejection Incidence and Severity | Weekly for the first month, monthly for the first year, quarterly until end of study (month 60) | The total number of Biopsy-Proven Acute Rejection (BPAR) episodes per patient and their severity as graded by the Banff VCA classification. |
| Mean days to Reversibility of Acute Rejection | Weekly for the first month, monthly for the first year, quarterly until end of study (month 60) | Measured by the Time to Clinical Resolution, defined as the number of days from the initiation of anti-rejection therapy to the return of the allograft to baseline clinical appearance and/or a follow-up biopsy showing a lower Banff grade or resolution. |
| Number of participants with Chronic Allograft Rejection (CLAD/CAV): | Weekly for the first month, monthly for the first year, quarterly until end of study (month 60) | Number of participants with Chronic Allograft Vasculopathy (CAV) or chronic skin changes as identified via protocol-driven histopathology. |
Countries
United States
Contacts
CONTACTOmowunmi Afolabi, MSc. Psychology
PRINCIPAL_INVESTIGATORBohdan Pomahac, MD
Yale University
PRINCIPAL_INVESTIGATORVijay Gorantla, MD, PhD, FRCS
Wake Forest University Health Sciences
Outcome results
None listed