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出境医 / 临床实验 / Validation of a Process for the Manufacture of Stem Cells Isolated From the Nasal Cavity for Innovative Cell Therapy of Traumatized Peripheral Nerves (NOSE)

Validation of a Process for the Manufacture of Stem Cells Isolated From the Nasal Cavity for Innovative Cell Therapy of Traumatized Peripheral Nerves (NOSE)

Study Description
Brief Summary:

Despite progress in the time taken to take charge and in the quality of the surgical technique, the repair of damaged peripheral nerves has not improved in the last twenty years. Faced with these limitations of surgical treatment, multidisciplinary teams from Marseille and Rouen have come together to propose an innovative approach to cell therapy that can limit inflammation and improve axonal growth.

Cell transplantation now appears as an alternative to treat nerve damage. Scientific advances have shown in animal models as well as in humans that mesenchymal stem cells are good cellular candidates for supporting nerve regeneration after transplantation. On the other hand, their collection requires an invasive sample most often of bone marrow. A new stem cell candidate capable of stimulating nerve regeneration has recently been identified in the olfactory mucosa located in the nasal cavity. These cells are part of the "ecto-mesenchymal" stem cell family. They have biological characteristics very similar to those of mesenchymal stem cells of the bone marrow.

They exhibit high mitogenic activity and have a high potential for differentiation towards neural lineages. Given their properties and ease of access within the nasal cavity, ecto-mesenchymal stem cells offer new perspectives for cell therapy targeting nerve damage.

In this context, nasal ecto-mesenchymal stem cells represent an interesting reconstruction alternative, particularly in the indication of peripheral nerve lesions. They are directly and easily accessible to any individual. We therefore propose in this study to validate a method of manufacturing isolated stem cells from a biopsy of a few cubic millimeters of the nasal cavity of adults, taken during a surgical procedure, with a view to proposing shortly an innovative cell therapy. From each nasal biopsy taken, the cells will be amplified in vitro under pharmaceutical grade conditions and then controlled, validated and characterized in particular for their ability to differentiate into neural cells and for their lack of genetic instability. The cells will also be cryo-preserved and then thawed under pharmaceutical grade conditions in order to validate the maintenance of their quality after cryopreservation allowing to propose a delayed implantation according to the clinical context. This study requires the taking of 25 biopsies of nasal mucosa taken from adults to document the reproducibility of the manufacturing process and possible inter-donor variations. This validation data is an essential step before considering a clinical trial of Innovative Cell Therapy Drugs.


Condition or disease Intervention/treatment Phase
Septoplasty Turbinoplasty Procedure: biopsy of mucosa's olfactory Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Validation of a Process for the Manufacture of Stem Cells Isolated From the Nasal Cavity for Innovative Cell Therapy of Traumatized Peripheral Nerves
Actual Study Start Date : December 10, 2018
Estimated Primary Completion Date : February 10, 2021
Estimated Study Completion Date : August 10, 2021
Arms and Interventions
Arm Intervention/treatment
patients with biopsy Procedure: biopsy of mucosa's olfactory
intervention under general or local anesthesia

Outcome Measures
Primary Outcome Measures :
  1. absence of caryotipic abnormalities during their amplification [ Time Frame: 24 months ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Major adults men or women
  • Affiliated to a social security scheme.
  • Absence of contraindication to general and / or local anesthesia
  • Relevant to an operative indication of functional surgery of the nose (septoplasty and / or turbinoplasty)

Exclusion Criteria:

  • Patients with proven organic pathologies of the nervous system
  • Pregnant and / or lactating women
  • Persons deprived of their liberty
  • Major under guardianship
  • persons unable to read the information document.
  • Patients with chronic inflammatory and / or infectious rhinosinusitis
  • Patient under antithrombotic therapy
  • Patient with hypersensitivity to local amide-bound anesthetics (such as lidocaine) or to any of the components, including methyl parahydroxybenzoate contained in the vehicle.
  • Patient with porphyria.
  • Patient with epilepsy not controlled by treatment.
  • Patient with a history of surgery on the ethmoid and / or the average turbinate bilaterally.
  • Patient with a history of cervico-cephalic radiotherapy
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Patrick DESSI 33(0)4 91 43 55 20 patrick.dessi@ap-hm.fr

Locations
Layout table for location information
France
Service d'Oto-Rhino-Laryngologie - Conception - AP-HM Recruiting
Marseille, France, 13354
Contact: Patrick DESSI    33(0)4 91 43 55 20    patrick.dessi@ap-hm.fr   
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
Layout table for investigator information
Study Director: Jean-Olivier ARNAUD AP-HM
Tracking Information
First Submitted Date  ICMJE July 11, 2019
First Posted Date  ICMJE July 16, 2019
Last Update Posted Date July 16, 2019
Actual Study Start Date  ICMJE December 10, 2018
Estimated Primary Completion Date February 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
absence of caryotipic abnormalities during their amplification [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Validation of a Process for the Manufacture of Stem Cells Isolated From the Nasal Cavity for Innovative Cell Therapy of Traumatized Peripheral Nerves
Official Title  ICMJE Validation of a Process for the Manufacture of Stem Cells Isolated From the Nasal Cavity for Innovative Cell Therapy of Traumatized Peripheral Nerves
Brief Summary

Despite progress in the time taken to take charge and in the quality of the surgical technique, the repair of damaged peripheral nerves has not improved in the last twenty years. Faced with these limitations of surgical treatment, multidisciplinary teams from Marseille and Rouen have come together to propose an innovative approach to cell therapy that can limit inflammation and improve axonal growth.

Cell transplantation now appears as an alternative to treat nerve damage. Scientific advances have shown in animal models as well as in humans that mesenchymal stem cells are good cellular candidates for supporting nerve regeneration after transplantation. On the other hand, their collection requires an invasive sample most often of bone marrow. A new stem cell candidate capable of stimulating nerve regeneration has recently been identified in the olfactory mucosa located in the nasal cavity. These cells are part of the "ecto-mesenchymal" stem cell family. They have biological characteristics very similar to those of mesenchymal stem cells of the bone marrow.

They exhibit high mitogenic activity and have a high potential for differentiation towards neural lineages. Given their properties and ease of access within the nasal cavity, ecto-mesenchymal stem cells offer new perspectives for cell therapy targeting nerve damage.

In this context, nasal ecto-mesenchymal stem cells represent an interesting reconstruction alternative, particularly in the indication of peripheral nerve lesions. They are directly and easily accessible to any individual. We therefore propose in this study to validate a method of manufacturing isolated stem cells from a biopsy of a few cubic millimeters of the nasal cavity of adults, taken during a surgical procedure, with a view to proposing shortly an innovative cell therapy. From each nasal biopsy taken, the cells will be amplified in vitro under pharmaceutical grade conditions and then controlled, validated and characterized in particular for their ability to differentiate into neural cells and for their lack of genetic instability. The cells will also be cryo-preserved and then thawed under pharmaceutical grade conditions in order to validate the maintenance of their quality after cryopreservation allowing to propose a delayed implantation according to the clinical context. This study requires the taking of 25 biopsies of nasal mucosa taken from adults to document the reproducibility of the manufacturing process and possible inter-donor variations. This validation data is an essential step before considering a clinical trial of Innovative Cell Therapy Drugs.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Septoplasty
  • Turbinoplasty
Intervention  ICMJE Procedure: biopsy of mucosa's olfactory
intervention under general or local anesthesia
Study Arms  ICMJE patients with biopsy
Intervention: Procedure: biopsy of mucosa's olfactory
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 10, 2021
Estimated Primary Completion Date February 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Major adults men or women
  • Affiliated to a social security scheme.
  • Absence of contraindication to general and / or local anesthesia
  • Relevant to an operative indication of functional surgery of the nose (septoplasty and / or turbinoplasty)

Exclusion Criteria:

  • Patients with proven organic pathologies of the nervous system
  • Pregnant and / or lactating women
  • Persons deprived of their liberty
  • Major under guardianship
  • persons unable to read the information document.
  • Patients with chronic inflammatory and / or infectious rhinosinusitis
  • Patient under antithrombotic therapy
  • Patient with hypersensitivity to local amide-bound anesthetics (such as lidocaine) or to any of the components, including methyl parahydroxybenzoate contained in the vehicle.
  • Patient with porphyria.
  • Patient with epilepsy not controlled by treatment.
  • Patient with a history of surgery on the ethmoid and / or the average turbinate bilaterally.
  • Patient with a history of cervico-cephalic radiotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patrick DESSI 33(0)4 91 43 55 20 patrick.dessi@ap-hm.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04020367
Other Study ID Numbers  ICMJE 2018-40
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique Hopitaux De Marseille
Study Sponsor  ICMJE Assistance Publique Hopitaux De Marseille
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jean-Olivier ARNAUD AP-HM
PRS Account Assistance Publique Hopitaux De Marseille
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP