Clinical Trial of Stem Cell Based Tissue Engineered Laryngeal Implants

NCT01977911 | Withdrawn Phase 1 DMC

• 2 other identifiers: UCL RD & ID no. 12/03312013-004359-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Disorder of Upper Respiratory System; Laryngostenosis; Tracheal Stenosis

Keywords

Airway reconstruction; Regenerative medicine

Outcome Measures

Primary Outcomes (1)

• Safety of tissue engineered laryngotracheal replacement

  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

  24 months post operative follow up

Secondary Outcomes (1)

• Efficacy of tissue engineered laryngotracheal replacement

  24 months post operative follow up

Other Outcomes (1)

• Cost effectiveness of tissue engineered laryngotracheal replacement

  24 months post operative follow up

Study Arms (1)

Tissue engineered airway construct

EXPERIMENTAL

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

Interventions

Stem cell based tissue engineered partial laryngeal implants OTHER

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.

Also known as: Tissue engineered partial laryngeal replacement graft, Tissue engineered epithelial cell layer when validated

Tissue engineered airway construct

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University College, London: lead
• Medical Research Council: collaborator

Study Sites (1)

University College London NHS Foundation Trust (UCLH)

London, NW1 2PG, United Kingdom

Location

Related Publications (2)

• Hamilton N, Bullock AJ, Macneil S, Janes SM, Birchall M. Tissue engineering airway mucosa: a systematic review. Laryngoscope. 2014 Apr;124(4):961-8. doi: 10.1002/lary.24469. Epub 2013 Nov 19.

  PMID: 24129819 BACKGROUND

• Culme-Seymour EJ, Mason K, Vallejo-Torres L, Carvalho C, Partington L, Crowley C, Hamilton NJ, Toll EC, Butler CR, Elliott MJ, Birchall MA, Lowdell MW, Mason C. Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series. Tissue Eng Part A. 2016 Feb;22(3-4):208-13. doi: 10.1089/ten.TEA.2015.0283. Epub 2015 Dec 24.

  PMID: 26559535 DERIVED

MeSH Terms

Conditions

Laryngostenosis; Tracheal Stenosis

Condition Hierarchy (Ancestors)

Laryngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Respiratory System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Tracheal Diseases

Study Officials

• Martin Birchall, Prof

  University College London (UCL) Ear Institute; Royal National Throat, Nose and Ear Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: April 1, 2018
• Primary Completion: May 25, 2018
• Study Completion: May 25, 2018
• Last Updated: June 6, 2018

Record last verified: 2018-06

Locations

GB (1)