Clinical Trial: Clinical Trial of Stem Cell Based Tissue Engineered Laryngeal Implants

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I/IIa Clinical Trial of Stem Cell Based Tissue Engineered Partial Laryngeal Implants in 10 Adult Patients With End-stage Laryngeal Stenosis With 24 Months Follow-up.

Brief Summary:

This study aims to test a new groundbreaking treatment for narrowing of the voicebox and upper windpipe, which can be due to injury, inflammatory disease or cancer treatment. Narrowing of the voicebox or upper windpipe can leave patients dependant on a tracheostomy tube to breath through (a tube or hole in the neck), which can require a high level of care with regular hospital visits and can lead to recurrent chest infections. Regular surgical procedures may be necessary to widen the airway. Speaking may be very difficult or not even possible, breathing is usually a struggle and swallowing can also be affected. Patients feel very tired all the time.

The new treatment tested by this study is an implant that will partially replace the voicebox or upper windpipe in order to cure the narrowing. The implant is based on a human donor voicebox or windpipe that has been processed with detergents and enzymes in order to remove all the cells from the donor, leaving a 'scaffold' of connective tissue. The patient's own stem cells are removed from the bone marrow, then are grown on the scaffold in the laboratory. These cells will form the cartilage in the wall of the scaffold. A split skin graft from the patient may be needed to line the inside of the implant. The implant can be considered 'living' due to the cells grown on it, and this type of treatment is referred to as 'tissue engineering' or 'regenerative medicine'.

Once these cells have attached and started to grow on the scaffold, it is ready to be implanted into the patient, and an operation is performed which occurs in two separate stages. The final stage of the operation involves removing the narrow section of voicebox or upper windpipe and implanting the scaffold to reconstruct it. Patients will be followed up for two years after this operation, with investigations such as CT

Detailed Summary:

The RegenVOX trial is a phase I/IIa safety and potential efficacy clinical trial of tissue-engineered laryngotracheal replacement using autologous-derived cells and decellularised human donor scaffolds in 10 patients with severe acquired laryngotracheal stenosis.

Current solutions for the treatment of advanced structural disorders of the larynx such as trauma, inflammatory disorders or following cancer treatment are suboptimal and patients with such problems require frequent hospitalisation. A regenerative solution that restores the anatomy of the larynx would provide a definitive treatment for these patients, improve the outcome of resection for malignant disease, avoid some laryngectomies and would reduce the threshold for performing surgery over administering chemotherapy thereby reducing morbidity. Giving patients a once-only therapy of a life-time functional living replacement would allow patients to lead tracheostomy-free lives with improved breathing, swallowing and speech and a lower requirement for hospital follow-up.

This project is a clinical trial of tissue engineered partial laryngeal replacements in 10 patients with end-stage laryngeal stenosis. The intervention is based on a human donor graft scaffold which is decellularised and then seeded with autologous mesenchymal stem cell-derived chondrocytes externally. Following expansion of these cells ex-vivo, the graft is implanted. This is the first clinical trial to our knowledge of a stem-call based organ replacement.

Inclusion criteria are:

Patients aged >=18 years with sufficient numbers of Mesenchymal Stromal Cells (MSCs) in their human Bone Marrow (hBM) aspirate.

Patients with Myer-Cotton Grade 3 or 4 laryn
Sponsor: University College, London

Current Primary Outcome: Safety of tissue engineered laryngotracheal replacement [ Time Frame: 24 months post operative follow up ]

The primary outcome measure is safety of the tissue engineered implant as defined by morbidity and mortality and measured by occurrence of adverse events throughout 24 months post operative follow up


Original Primary Outcome: Safety of tissue engineered lyryngotracheal replacement [ Time Frame: 24 months post operative follow up ]

The primary outcome measure is safety of the tissue engineered implant as defined by morbidity and mortality and measured by occurrence of adverse events throughout 24 months post operative follow up


Current Secondary Outcome: Efficacy of tissue engineered laryngotracheal replacement [ Time Frame: 24 months post operative follow up ]

Secondary outcome is efficacy as determined

  1. Absence of tracheostomy.
  2. Absence of non-absorbable stent.
  3. Improvement in mean airway diameter.
  4. Improvement in Forced Expiratory Volume in 1 second (FEV1).
  5. Improvement in global quality of life (EQ-5D).
  6. Improvement in maximum phonation time (MPT) as measured by Voice Analysis Operavox (VAO).
  7. Improvement in self assessment of voice handicap (VHI-10).
  8. Improvement in swallowing function (EAT-10).
  9. Improvement in airway, dyspnoea, voice, swallowing index (ADVS index).
  10. Improvement in the penetration-aspiration scale (PAS) as per Video Fluoroscopic Swallow (VFS) or Functional Endoscopic Evaluation of Swallowing (FEES).

Health Economics



Original Secondary Outcome: Efficacy of tissue engineered lyryngotracheal replacement [ Time Frame: 24 months post operative follow up ]

Secondary outcome is efficacy as defined by absence of tracheostomy tube, absence of stent, improvement in mean airway diameter, improvement in FEV1, improvement in Global Quality of life (SF-12 Health Survey), improvement in maximum phonation time (MPT) and improvement in self-assessment of voice handicap (VHI-10).


Information By: University College, London

Dates:
Date Received: October 31, 2013
Date Started: August 2015
Date Completion: December 2018
Last Updated: November 25, 2015
Last Verified: August 2015