Laryngeal Allograft Transplantation

Study Overview
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Brief Summary
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The purpose of this proposed study is to obtain safety and efficacy data on human laryngeal allograft transplantation in an effort to safely use these procedures as a viable reconstructive option for patients with severe laryngeal or laryngotracheal incompetence.

Detailed Description
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Patients with severe laryngeal or laryngotracheal incompetence without other reconstructive options will be considered for cadaveric laryngotracheal transplantation. Data will be collected from 10 patients and will include length of hospital stay, short-term complications, long-term complications, hospital readmission, return trips to the operating room (OR), rejection episodes and severity, swallowing function, ability to have tracheotomy tube decannulated, voice parameters, pulmonary function, development of anti-donor antibodies, and quality of life scores.

Official Title
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A Prospective Nonrandomized Study of Laryngeal Allograft Transplantation Clinical Investigation

Conditions
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Larynx Stenosis, Larynx Disease, Laryngectomy, Larynx, Larynx Fracture

Intervention / Treatment
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* Procedure: Larynx Allograft Transplantation


Participation Criteria
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Eligibility Criteria
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Potential subjects for this study include patients with severe laryngeal dysfunction or a previous laryngectomy. For the purposes of this study, severe laryngeal dysfunction is defined as the loss of normal laryngeal function resulting in significant dysphonia, dysphagia, or dyspnea. Inclusion Criteria: Ages 18 years and older Male or Female One of the following: Severe laryngeal dysfunction as described above Laryngeal stenosis 5 years or longer s/p definitive management for head and neck cancer Laryngeal cancer requiring total laryngectomy in a patient already on immunosuppression Low-grade chondrosarcoma requiring total laryngectomy Ability to obtain informed consent from the patient Exclusion Criteria: Poor surgical candidacy secondary to poor physical/mental health as determined by a pre-operative medical evaluation General medical status Pregnancy Any systemic disease which would alter life expectancy Active neoplastic disease, not considered yet to be cured (Exceptional cases will be considered in case by case discussion)Less than 5 years s/p definitive management for cancer Cancer within the last 5 years (Exceptional cases will be considered in case by case discussion) Obesity (Body Mass Index >29 - 30)(Exceptional cases will be considered on a case by case basis) Cachexia (BMI<18)(Exceptional cases will be considered on a case by case basis) Significant renal dysfunction (Creatinine clearance < 50 ml/min.) Significant hepatic dysfunction Significant kidney damage Unmanageable infections Unable to participate in preoperative exercise training Unable to be weaned to equal or less than 10 mg/day of steroids Untreatable cardiac disease Active neuromuscular disease History of recurrent aspiration or active, unmanageable Gastro-Esophageal Reflux Patients with active connective tissue diseases (exceptions to be considered in a case by case basis) Patients unable to achieve > 600 feet in a 6 minute walk test (exceptions to be considered in a case by case basis) Patients considered having active immunodeficiency disorders (exceptions to be considered in a case by case basis) Multiple co-morbidities that would make transplantation prohibitively risky Psychosocial parameters Severe mental retardation, psychosis, depression or organic brain syndrome Uncontrolled diabetes mellitus. Once HbA1C < 7, reevaluate for candidacy. Active substance use within 6 months Active smoking within 6 months Active alcoholism within 6 months Inability to comply with transplant-related management and medical follow-up Any other circumstances that deem the candidate high risk from a psychosocial perspective

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Larynx Allograft Transplantation<br>Cadaveric laryngotracheal transplantation | Procedure: Larynx Allograft Transplantation<br>* This study is a prospective clinical trial designed to assess the efficacy and safety of laryngeal transplantation. A total of 10 patients will be enrolled over a five-year timeframe. Study length is 5 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival of the allograft at the one-year visit. | Survival of the allograft as indicated by histological rejection grading. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Swallowing without aspiration at the one-year visit. |  | 1 year | 
| Voice Evaluation | Standard voice evaluation will include voice recordings, acoustic and aerodynamic measurements as compared to baseline measurements. | 1 year | 
| Pulmonary function | Pulmonary function values within normal range. | 1 year | 
| Ability to have tracheotomy tube decannulated | Ability to have tracheotomy tube decannulated after successful capping trials. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe laryngotracheal dysfunction