Functional Recovery, Upper Extremity Vascularized Composite Allotransplantation
Conditions
Keywords
Composite tissue allotransplantation, Rehabilitation, Vascularized composite allotransplantation, Upper-extremity transplantation, Hand transplantation
Brief summary
The primary objective of this study is to evaluate the 5-year (60-month) allograft survival rate of upper extremity vascularized composite allotransplantation performed under the standardized CONSORT clinical protocol.
Detailed description
The study population includes adults with severe upper extremity disfigurement meeting the following criteria: * Anatomic Severity: Loss of upper extremity proximal to the wrist (including transhumeral and shoulder-level levels when clinically appropriate) * Refractory Status: prosthesis delivered unsatisfactory results
Interventions
PROCEDUREUpper Extremity Vascularized Composite Allotransplantation (VCA)
Upper Extremity 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. where feasible, to support psychosocial and aesthetic integration. * Willingness to undergo comprehensive psychosocial evaluation and ongoing monitoring by the multidisciplinary team. * Demonstrated motivation for transplantation and understanding of the investigational nature of upper extremity 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 upper extremity disfigurement involving amputation proximal to the wrist. * Conventional restorative options, including advanced myoelectric or body-powered prostheses, must be documented as exhausted (defined as a minimum of 12 months of consistent use of myoelectric or body-powered prostheses with a QuickDASH score remaining above 30), infeasible (due to stump length or soft tissue coverage), or clinically inadequate for restoring the sensory-motor integration required for the participant's essential functional needs. * 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). * Upper extremity anatomy suitable for transplant (no significant upper extremity trauma, major congenital anomalies, or prior upper extremity 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. * Known history of cancer, especially head/neck or hematologic malignancy. * Permanent upper extremity tattoos or highly identifiable markings judged incompatible with the recipient's preferences or the clinical/ethical judgment of the transplant team. * History of extremity 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 upper extremity 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 |
|---|---|---|
| Mean Active Range of Motion | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Measured in degrees for the transplanted joint (the elbow (in some occasions), the wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints). |
| Muscle strength assessed using Clinical Motor Grading (MRC Scale) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Medical Research Council (MRC) Scale is a standardized 0-to-5 manual muscle testing system used by clinicians to grade muscle strength and motor power. Motor strength was graded on a scale from M0 to M5, where M0 indicates no visible muscle contraction and M5 indicates normal muscle strength against full resistance |
| Mean Grip Strength | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Quantified in kilograms (kg) using a calibrated hand dynamometer |
| Mean Pinch Strength | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Quantified in kilograms (kg) using a calibrated pinch gauge |
| Carroll Upper Extremity Function Test (UEFT) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | A validated composite score of 33 tasks used to measure overall functional capability. Uses a 0 to 3 scale for individual task performance:0 points: Cannot complete any portion.1 point: Completes part of the test item.2 points: Completes the item slowly or clumsily.3 points: Completes the item fully and normally.Yields a cumulative score up to 99 for the dominant hand and 96 for the non-dominant hand |
| 9-Hole Peg Test (9-HPT) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Measured in seconds to quantify manual dexterity and fine motor coordination. |
| Sensory Detection Thresholds assessed using Semmes-Weinstein monofilament test | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Evaluates light touch thresholds and protective sensation loss in hands, feet, or limbs. Determined by the minimum size of Semmes-Weinstein monofilament perceived by the patient. |
| Tactile Acuity (2PD) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Measured by Static Two-Point Discrimination in millimeters (mm). |
| 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 LIMB-QOL Resilience, Self Care and Fine Motor | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | Evaluates resilience, self care and fine motor following major extremity injury. Higher scores reflect a more positive outcome. Scored on a T-score metric with a mean of 50 and a standard deviation of 10. |
| Mean score Upper Extremity Disability (QuickDASH) | Baseline, 3, 6, 12, 24, 36, 48 and 60 months | An 11-item self-reported tool measuring upper extremity physical function and symptoms. Scores range from 0 (no disability) to 100 (most severe disability). |
| 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