Clinical Trial of Stem Cell Based Tissue Engineered Laryngeal Implants (RegenVOX)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2014 by University College, London
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01977911
First received: October 31, 2013
Last updated: December 5, 2014
Last verified: December 2014
  Purpose

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 scans, examination of the voicebox and windpipe with a flexible camera (bronchoscopy) and blood tests performed at specific times.

It is intended that this treatment will significantly improve patients' symptoms resulting in better breathing, swallowing and voice function, reducing the need for repeated hospital visits and procedures and enhancing patients' quality of life.


Condition Intervention Phase
Disorder of Upper Respiratory System
Laryngostenosis
Tracheal Stenosis
Other: Stem cell based tissue engineered partial laryngeal implants
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Further study details as provided by University College, London:

Primary Outcome Measures:
  • Safety of tissue engineered laryngotracheal replacement [ Time Frame: 24 months post operative follow up ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Efficacy of tissue engineered laryngotracheal replacement [ Time Frame: 24 months post operative follow up ] [ Designated as safety issue: No ]

    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



Other Outcome Measures:
  • Cost effectiveness of tissue engineered laryngotracheal replacement [ Time Frame: 24 months post operative follow up ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 10
Study Start Date: April 2015
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tissue engineered airway construct

Stem cell based tissue engineered partial laryngeal implants:

The final experimental product is a highly tested, recellularised, stem cells based tissue engineered product (airway construct) for operative partial laryngeal implantation into patients with severe laryngotracheal stenosis

Other: Stem cell based tissue engineered partial laryngeal implants
Stem cells from the patient receiving the implant are removed from the bone marrow, and are then 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'. Once these cells have attached and started to grow on the scaffold, it is ready to be implanted into the patient and a two separate operative stages can occur. The final stage of the operation involves removing the narrow section of voicebox or upper windpipe and implanting the scaffold to reconstruct it.
Other Names:
  • Tissue engineered partial laryngeal replacement graft
  • Tissue engineered epithelial cell layer when validated

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients aged >=18 years with sufficient numbers of Mesenchymal Stromal Cells (MSCs) in their 8-10ml human Bone Marrow (hBM) aspirate.

Patients with Myer-Cotton Grade 3 or 4* laryngotracheal stenosis or equivalent due to traumatic, inflammatory, iatrogenic, or idiopathic causes who have exhausted conventional therapies.

*The Myer-Cotton grading system for mature, firm, circumferential stenosis, confined to the subglottis describes the stenosis based on the per cent relative reduction in cross-sectional area of the subglottis. Four grades of stenosis:

  • grade 1 lesions have less than 50% obstruction
  • grade 2 lesions have 51% to 70% obstruction
  • grade 3 lesions have 71% to 99% obstruction
  • grade 4 lesions have no detectable lumen or complete stenosis

Exclusion Criteria:

  • Pregnancy
  • Patients positive for HIV 1, HIV 2, HCV, HBV, syphilis or HTLV
  • Those unable to provide informed consent
  • Co-morbid severe chronic obstructive pulmonary disease (according to NICE criteria)
  • Patients with active / uncontrolled chronic inflammatory conditions such as granulomatosis with polyangitis (formerly Wegener's granulomatosis) and sarcoidosis
  • 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, or low grade airway malignancy such as chondrosarcoma which may be causing airway obstruction)
  • Life expectancy less than 5 years unless this limitation is principally due to the airway obstruction to be treated
  • Concurrent enrollment in any other Clinical Trial of Investigational Medicinal Product (CTIMP).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01977911

Contacts
Contact: Rinat Ezra, PhD +44 (0) 2076790924 regenvox@ucl.ac.uk
Contact: Hayley Herbet, MBChB, FRACS regenvox@ucl.ac.uk

Locations
United Kingdom
University College London NHS Foundation Trust (UCLH) Not yet recruiting
London, United Kingdom, NW1 2PG
Principal Investigator: Martin Birchall, Prof         
Sponsors and Collaborators
University College, London
Medical Research Council
Investigators
Principal Investigator: Martin Birchall, Prof University College London (UCL) Ear Institute; Royal National Throat, Nose and Ear Hospital
  More Information

Additional Information:
Publications:
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01977911     History of Changes
Other Study ID Numbers: UCL RD & ID no. 12/0331, 2013-004359-18
Study First Received: October 31, 2013
Last Updated: December 5, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
Airway reconstruction
Regenerative medicine

Additional relevant MeSH terms:
Laryngostenosis
Tracheal Stenosis
Congenital Abnormalities
Laryngeal Diseases
Otorhinolaryngologic Diseases
Respiratory System Abnormalities
Respiratory Tract Diseases
Tracheal Diseases

ClinicalTrials.gov processed this record on July 01, 2015