Face Transplant for Facial Disfigurement

Overseen By TBD TBD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Disqualifiers: HIV, Hepatitis, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 33

15 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the face transplant trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the study team to understand any potential interactions with the trial's immunomodulatory protocol.

What data supports the effectiveness of the treatment Pittsburgh Protocol/Starzl Protocol for face transplant in patients with facial disfigurement?

The treatment has shown success in restoring facial function and appearance, with patients experiencing improved quality of life and social reintegration. Despite serious complications, long-term outcomes have been positive, with near-normal recovery of motor and sensory functions. ^{1 2 3 4 5}

Is face transplant surgery generally safe for humans?

The available research articles do not provide specific safety data on face transplant surgery or related protocols like the Pittsburgh Protocol or Starzl Protocol. Therefore, no relevant safety information can be provided from these sources. ^{6 7 8 9 10}

How is the Pittsburgh Protocol treatment unique for face transplants?

The Pittsburgh Protocol is unique because it combines advanced microsurgery and immunology to restore both appearance and function in patients with severe facial disfigurements, offering a comprehensive approach that traditional reconstructive techniques cannot achieve. ^{3 4 11 12 13}

What is the purpose of this trial?

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.

Research Team

Damon Cooney, MD, PHD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-65 with severe facial injuries or defects, who are non-smokers and U.S. citizens or equivalent. They must not have psycho-social issues like drug abuse, active cancer in the past 5 years, or conditions affecting treatment outcomes. Women of childbearing age should agree to use contraception for a year post-transplant.

Inclusion Criteria

Negative crossmatch with donor

No co-existing psycho-social problems (i.e., alcoholism, drug abuse)

If female of child-bearing potential, consent to use reliable contraception for at least one year following transplantation

Exclusion Criteria

Positive for Hepatitis C

Patients considered unsuitable per the consulted Psychiatric/ Psychologic appraisal

A history of medical non-compliance

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo face transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning

1 month

Daily visits for the first 28 days

Post-operative Monitoring

Post-operative serum trough levels and graft survival are documented to monitor immunosuppression and graft health

5 years

Semiweekly Weeks 5-12, weekly Weeks 13-25, biweekly Weeks 26-38, monthly Months 10-12, quarterly Years 2-5

Follow-up

Participants are monitored for long-term safety and effectiveness after transplantation

5 years

Treatment Details

Interventions

• Pittsburgh Protocol/Starzl Protocol

Trial Overview The study tests a new protocol combining bone marrow cell therapy with low-dose immunosuppression (1-drug) to minimize side effects after face transplantation. It aims to safely restore facial function and appearance using fewer drugs over time.

Participant Groups

Group I: Treatment (Transplantation) Experimental Treatment 1 Intervention

Face transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning.

Pittsburgh Protocol/Starzl Protocol is already approved in United States for the following indications:

Approved in United States as Pittsburgh Protocol for:

• Face transplantation for devastating facial injuries/defects

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

Facial allotransplantation can lead to nearly normal sensory recovery, even without direct repair of sensory nerves, which is comparable to traditional nerve repair methods.

The surprising sensory recovery is attributed to factors like the preservation of receptor density in the allograft, regeneration from surrounding tissues, and the effects of immunosuppressive therapy with tacrolimus, which enhances nerve regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathways of sensory recovery after face transplantation. Siemionow, M., Gharb, BB., Rampazzo, A.[2022]

A digitally planned face transplant performed on a 55-year-old man resulted in near-normal recovery of motor and sensory functions, with the patient and his family expressing high satisfaction three years post-surgery.

Despite facing serious complications during the first year, the successful management of these issues and the use of a multidisciplinary team approach contributed to a positive overall outcome and social reintegration for the patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Multifunctional Outcome and Risks of Face Vascularized Composite Allotransplantation. Roche, NA., Blondeel, PN., Vermeersch, HF., et al.[2018]

In a study of six face transplant patients over 36 months, active coping strategies were linked to better mental health before the transplant, while avoidant strategies became protective after the transplant, suggesting a shift in coping effectiveness post-surgery.

The findings highlight the importance of assessing coping strategies before the transplant and providing coping training afterward, as these strategies can significantly influence long-term psychosocial outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In the face of change: Which coping strategies predict better psychosocial outcomes in face transplant recipients? Nizzi, MC., Pomahac, B.[2022]

Composite vascularized allotransplantation has revolutionized facial reconstructive surgery, allowing for true restorative procedures that can effectively address severe facial deformities that traditional methods cannot.

Facial transplants should be carefully planned to ensure comprehensive restoration of anatomy and function, with a focus on aesthetic units, and can range from small area restorations to full-face transplants for major defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From partial to full-face transplantation: total ablation and restoration, a change in the reconstructive paradigm. Barret, JP.[2022]

A systematic review of face transplantation literature revealed that critical protocols for patient care, such as immunosuppression and graft surveillance, are inconsistently reported, with only 61% of studies detailing antimicrobial prophylaxis and 75% covering immunosuppressive induction.

Standardized reporting of medical protocols is essential for improving patient outcomes in face transplantation, as these protocols are key to managing rejection and graft failure, yet only 43% of studies documented surgical strategies for graft failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting Practices on Immunosuppression and Rejection Management in Face Transplantation: A Systematic Review. Daneshgaran, G., Stern, CS., Garfein, ES.[2021]

A national database analysis of injection laryngoplasty (IL) identified 47 adverse events, confirming that while complications can occur, the procedure is generally safe, with only a few cases requiring emergency interventions.

The most common complications included laryngeal edema and persistent dysphonia, with calcium hydroxyapatite (CAHA) associated with a higher rate of adverse events compared to other materials like hyaluronic acid (HA) and carboxymethylcellulose (CMC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events following injection laryngoplasty: An analysis of the MAUDE database. Din-Lovinescu, C., Talmor, G., Gravina, A., et al.[2022]

Adverse event reporting in randomized clinical trials (RCTs) is often inadequate, leading to potential safety concerns for new drugs once they are used in larger, more diverse patient populations.

The article highlights specific shortcomings in AE reporting for tumor necrosis factor (TNF) inhibitors, including issues with time-to-event reporting, standardized incidence ratios, and insufficient sample sizes, which can obscure the true safety profile of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some concerns about adverse event reporting in randomized clinical trials. Yazici, Y.[2008]

The Aggregate Safety Assessment Plan (ASAP) is designed to enhance safety planning and ongoing data review throughout a drug's life-cycle, promoting a systematic approach to understanding product safety.

By implementing the ASAP process, drug developers can improve early detection of safety signals, better characterize risks, and ensure consistent safety messaging across studies, ultimately aiding in informed decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggregate Safety Assessment Planning for the Drug Development Life-Cycle. Hendrickson, BA., Wang, W., Ball, G., et al.[2021]

A 5-year review of Morbidity and Mortality Conferences in the Division of Rheumatology at SickKids identified 83 reported cases, with the majority related to miscommunication (34.9%) and treatment/test/procedure issues (22.9%).

The review led to 89 recommendations for system improvements, emphasizing that increased reporting of adverse events can enhance patient safety and healthcare quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trying to improve care: the Morbidity and Mortality Conference in a division of rheumatology. Batthish, M., Tse, SM., Feldman, BM., et al.[2014]

Biologics have significantly improved the management of rheumatoid arthritis (RA) by selectively targeting the immune system, leading to better disease control, but they also raise safety concerns among doctors.

While randomized controlled trials (RCTs) provide some safety insights, they often don't reflect real-world safety issues due to strict study designs; in contrast, registries offer more reliable long-term safety data, though there is a lack of such data from Eastern Europe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of biologics in rheumatoid arthritis: data from randomized controlled trials and registries. Codreanu, C., Damjanov, N.[2023]

Facial transplantation is a promising surgical option for patients who cannot achieve satisfactory results with traditional methods, but it requires careful matching of blood groups and human leukocyte antigens to minimize the risk of tissue rejection and complications from immunosuppression.

While the functional outcomes of facial transplantation show slow but encouraging recovery of motor and sensory functions, ethical concerns and uncertainties about long-term results currently limit its widespread application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial transplantation. An update of results and perspectives from tissue engineering. Simonacci, F., Toni, R., Raposio, E.[2022]

Face transplantation is a complex procedure that combines microsurgery and immunology to help individuals with severe facial disfigurements, and it requires thorough patient education to ensure informed consent and adherence to treatment.

A comprehensive 181-page handbook was developed to educate potential face transplant patients about the process, team members, and unique aspects of the procedure, addressing their concerns and enhancing their recovery and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Face time: educating face transplant candidates. Lamparello, BM., Bueno, EM., Diaz-Siso, JR., et al.[2021]

The computerized surgical planning (CSP) protocol significantly improved the execution of face transplants (FT), resulting in minor variations in cephalometric measurements and a reduction in operative time from 36 to 25 hours across three cases.

The use of CSP also decreased the need for cadaveric simulations prior to surgery, indicating enhanced planning efficiency and potentially better outcomes in both partial and full face transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized Approach to Facial Transplantation: Evolution and Application in 3 Consecutive Face Transplants. Ramly, EP., Kantar, RS., Diaz-Siso, JR., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pathways of sensory recovery after face transplantation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Long-Term Multifunctional Outcome and Risks of Face Vascularized Composite Allotransplantation. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

In the face of change: Which coping strategies predict better psychosocial outcomes in face transplant recipients? [2022]

4. United States pubmed.ncbi.nlm.nih.gov

From partial to full-face transplantation: total ablation and restoration, a change in the reconstructive paradigm. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Reporting Practices on Immunosuppression and Rejection Management in Face Transplantation: A Systematic Review. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events following injection laryngoplasty: An analysis of the MAUDE database. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Some concerns about adverse event reporting in randomized clinical trials. [2008]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Aggregate Safety Assessment Planning for the Drug Development Life-Cycle. [2021]

9. Canada pubmed.ncbi.nlm.nih.gov

Trying to improve care: the Morbidity and Mortality Conference in a division of rheumatology. [2014]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Safety of biologics in rheumatoid arthritis: data from randomized controlled trials and registries. [2023]

11. Italy pubmed.ncbi.nlm.nih.gov

Facial transplantation. An update of results and perspectives from tissue engineering. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Face time: educating face transplant candidates. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Computerized Approach to Facial Transplantation: Evolution and Application in 3 Consecutive Face Transplants. [2022]