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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to making face transplants safer and more effective for individuals with severe facial injuries or deformities. Researchers are testing a special treatment plan, known as the Pittsburgh Protocol or Starzl Protocol, which uses donor bone marrow cells to help the transplanted face survive with fewer drugs needed to prevent rejection. This approach might help individuals regain their appearance and better participate in social life. Suitable candidates include those who have had a major face injury, desire a face transplant, and are non-smokers. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 prior data suggests that this protocol is safe for face transplantation?

Research has shown that the Pittsburgh Protocol, also known as the Starzl Protocol, shows promising safety results in face transplant patients. In earlier studies, patients tolerated the protocol well, with positive outcomes in immune system responses. This method uses a new technique involving donor bone marrow cells, reducing the need for many immunosuppressive drugs.

Another study found that the protocol effectively managed the body's reaction to the transplant, crucial for preventing rejection. While more long-term data is needed, results so far suggest that the side effects are manageable. This method aims to lower the high doses of medication usually required after a transplant, which can lead to infections or other serious health issues.

Overall, the Pittsburgh Protocol is promising because it may make face transplants safer for more people by reducing these risks. However, since this is a Phase 2 trial, the treatment is still being tested to gather more detailed safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard facial reconstruction methods, which often involve multiple surgeries and prosthetics, face transplantation in this protocol offers a more comprehensive and potentially transformative solution. This treatment is unique because it combines face transplantation with a new donor bone marrow cell-based therapy, reducing the need for multiple immunosuppressant drugs. Researchers are excited about the possibility of patients eventually weaning off immunosuppression, which could minimize long-term health risks and improve overall quality of life for those with severe facial disfigurement.

What evidence suggests that the Pittsburgh Protocol is effective for face transplantation?

Studies have shown that face transplants can lead to significant improvements in both function and appearance. More than 20 face transplants have been successfully completed. However, the risk of the body rejecting the transplant remains a major challenge, necessitating lifelong medication to prevent rejection. This trial tests the Pittsburgh Protocol, a new method that aims to reduce these risks by combining donor bone marrow cells with lower doses of medication. This approach has shown promise in helping the transplant survive with fewer side effects, potentially making face transplants safer and more accessible. ^{1 2 6 7 8}

Who Is on the Research Team?

Damon Cooney, MD, PHD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-3-congenital-abnormalities-7-2012-97b0f

Face Transplant for Facial Disfigurement This Phase 2 medical study run by Johns Hopkins University is evaluating whether Pittsburgh Protocol/Starzl Protocol will have tolerable side effects ...

2. hopkinsmedicine.org hopkinsmedicine.org/plastic-reconstructive-surgery/research/clinical-trials

Clinical Trials This non-randomized, Phase II clinical trial will document the use of a new immunomodulatory protocol (aka - Pittsburgh Protocol, Starzl Protocol) for ...

3. stiresearch.health.pitt.edu stiresearch.health.pitt.edu/research/

Research - Starzl Transplantation Institute In a little over 50 years, solid organ transplantation has become a common life-saving procedure that is performed more than 100,000 times per ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11235358/

Immunosuppressive strategies in face and hand transplantation Episodes of rejection were reported in 60 (65.9%) of hand- and 33 (73%) of face transplant patients respectively. Graft loss of 12 (13.2%) hand and 4 (8.9%) ...

5. secure.arkansasbluecross.com secure.arkansasbluecross.com/members/report.aspx?policyNumber=2013011&viewIntro=yes

Transplant, Composite Tissue Allotransplantation, Hand ... Ongoing Clinical Trials​​ It will test the “Pittsburgh Protocol”, an immunomodulatory strategy using donor bone marrow stem cells. Recipients will be selected ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/jso.25147

Innovations in reconstructive microsurgery ... The protocol was well tolerated by the patients with satisfying immunologic outcomes.68 Long-term data should validate the use of TAC ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7489595/

Anesthetic Considerations in Facial Transplantation This study presents an institutional anesthesia protocol, defines reported anesthetic considerations, and provides a comprehensive update to inform future ...

8. library.pitt.edu library.pitt.edu/balancing-physician-autonomy-and-oversight-case-study-dr-thomas-e-starzl-and-development-organ

A Case Study of Dr. Thomas E Starzl and the Development ... This case study provides excellent context for a discussion into the degree of autonomy we grant physicians to make ethical decisions in compassionate use ...