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RegenVOX

RegenVOX: Clinical trial of a voicebox implant using tissue engineering

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.

UCL Ear Institute: http://www.ucl.ac.uk/ear/about-the-ear-institute/participate/RegenVOX/

Should you wish to take part in the study, or if you would like to receive more information, please contact the Research Nurse, Binitha Paruthickal: b.paruthickal@ucl.ac.uk or the Clinical Research Associate, Katerina Tsagkovits: k.tsagkovits@ucl.ac.uk.


RegenVOX overview:

Patients with narrowing of the larynx or upper trachea may be dependent on a tracheostomy tube to breathe through (a tube going through a hole in the neck). 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 that will be tested in this trial is an implant that will partially replace the larynx or upper trachea with the aim of improving the narrowing. The implant is based on tissue from a deceased human donor that has been cleaned to remove all the cells from the donor. A connective tissue framework is left behind, which is described as a ‘scaffold’. 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. 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'.

The scaffold along with the patient’s own living cells is surgically implanted one month later. Initially it is implanted into a muscle in the forearm (although it could also be implanted into the neck, chest wall or other site such as the leg or foot) so that it can develop a good blood supply. Between 2 and 3 months later, a second operation is performed and the implant along with its new blood supply is moved and used to reconstruct your larynx or upper trachea.

Unlike an organ transplant, anti-rejection drugs are not necessary because the donor cells have been removed in the cleaning process and patient’s own stem cells have been grown on the scaffold to replace them.

The treatment is intended to improve breathing, swallowing and voice symptoms but we do not know how successful this will be. That is why we are carrying out this research.

Two hospital sites have been activated and are currently recruiting:

  • Royal National Throat Nose Ear Hospital under Professor Martin Birchall
  • Charing Cross Hospital under Mr Guri Sandhu

Should you wish to take part in the study, or would like to receive more information, please contact the Research Nurse, Binitha Paruthickal: b.paruthickal@ucl.ac.uk or the Clinical Research Associate, Katerina Tsagkovits: k.tsagkovits@ucl.ac.uk.

 

RegenVOX: Scientific 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-cell based organ replacement.

The primary outcome measure is safety as determined by morbidity and mortality as measured by occurrence of adverse events. Secondary outcome is efficacy as determined by

  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).

and Health Economics.

Patients will be followed up for 2 years within this study. Key milestones will be assessed at 6 and 12 months. The follow-up regimen includes bronchoscopy and airway brushings taken at 1 week post implantation and full physical assessment including CT imaging, pulmonary function tests, blood tests and bronchoscopy at 1, 6, 12, 18 and 24 months. Telephone follow-up will take place in between these assessments.

This trial will provide a level of insight into the real clinical potential for stem cell/tissue engineering combined technologies. We will also develop new pathways for maximising discovery science and health economic benefit from complex regenerative medicine therapies (a reverse translational route map), with important generic benefits for scientists and clinicians.

 

RegenVOX: Inclusion Criteria

  • Patients >=18 years of age with enough stem cells, which will be taken of their bone marrow at the screening visit, to enable the growth of the scaffold. Potential participants can refuse to provide stem cells at screening but this will result at screen failure.
  • Severe narrowing of the larynx and/or upper trachea (defined as narrowing of 70-100%)
  • Considered to be suitable for the trial by a specialist airway multi-disciplinary team

Exclusion Criteria

  • Pregnancy
  • Those unable to provide informed consent
  • HIV, hepatitis B, hepatitis C, syphilis or HTLV infection (according to national regulations for patients receiving tissue engineered treatments)
  • Severe Chronic Obstructive Pulmonary Disease (COPD)
  • Active / uncontrolled inflammatory disease (e.g. Wegener’s granulomatosis)
  • Any current or previous cancer within 5 years (except non-melanoma skin cancer, adequately treated carcinoma in situ of the uterine cervix, laryngeal malignancy treated locally with no local recurrence and no metastases (distant spread) and low grade airway tumours such as chondrosarcoma that may be causing airway obstruction)
  • Life expectancy less than 5 years unless this limitation is principally due to the airway obstruction to be treated

 

ClinicalTrials.gov Identifier: NCT01977911