in Vitro Evaluation of the Anti-fibrotic Activity of Adipose Tissu-derived Stromal Vascular Fraction Used as a Medicinal Treatment for Scarred Vocal Folds (CELLCORDES BIO)

in Vitro Evaluation of the Anti-fibrotic Activity of Adipose Tissu-derived Stromal Vascular Fraction Used as a Medicinal Treatment for Scarred Vocal Folds: Interest in the Definition of 'Potency' Markers and Optimized Cellular Engineering Trategies

This is a single-center, prospective study, aimed at investigating the anti-fibrotic in vitro activity of the stromal vascular fraction of patients with scarred vocal cord.

Study Overview

• Status: Not yet recruiting
• Conditions: Vocal Cord Injuries
• Intervention / Treatment: Other: Reuse of surgical waste; Other: Reuse of biological samples

Detailed Description

This single-center, prospective study will last 28 months and will be carried out in two stages:

1. Comparison of the in vitro anti-fibrotic activity and production/management circuit of different cell therapy products derived from adipose tissue obtained from healthy donors (n=8) [secondary objective] during the first 12 months of the project.
2. Evaluate the association between the in vitro anti-fibrotic activity of fraction vascular fraction (FVS) samples and the clinical improvement obtained with the same sample autologously injected into a patient in the CELLCORDES2 trial (minimum recruitment n=10, CELLCORDES2 biocollection) [primary objective]. This second stage will be carried out between M12 and M24 to optimize the number of patients to be included.

• Study Type: Observational
• Enrollment (Estimated): 18

Contacts and Locations

• Study Contact: Name: Clement PIERRE, PhD; Phone Number: +33491435796; Email: clement.pierre@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with scared vocal cord

Description

Inclusion criteria for patients included in the CELLCORDES 2 clinical trial

• Voice Handicap Index > 50/120
• Scarring, congenital (sulcus) or post-phonosurgery vocal cords
• Vibratory anomalies in the middle third of one or both vocal cords on stroboscopy
• A minimum of six months after the initial surgery
• Patients aged 18 to 70 years
• Good general health
• Negative pregnancy test and contraception for women of childbearing age Signature of consent for the storage and use of biological samples

Inclusion criteria for Healthy donnors:

• Liposuction surgery for aesthetic reasons
• BMI between 18 and 27
• No chronic diseases
• Non-opposition to the use of surgical waste for research purposes after freezing in a biological collection

Exclusion criteria: For all patients:

• Refusal or inability to comply with the study procedures
• Minors
• Pregnant or breastfeeding women
• Legally protected adults (under guardianship or curatorship)
• Individuals residing in a healthcare or social establishment emergency situations
• Individuals deprived of liberty
• Detainees
• Individuals not covered by a social security scheme
• Use of an experimental drug in the last three months
• Contraindication to local anesthesia
• Anticoagulant treatment
• Coagulation disorders (TP < 65%, TCA > 1.2)
• Premenopausal women of childbearing age without contraception
• Lack of or refusal of informed consent

Exclusion criteria for Patients in the CELLCORDES 2 clinical trial:

• Patients refusing pre- and post-operative speech therapy
• History of malignant lesions or severe dysplasia on the scarred vocal cord
• History of laryngeal papillomatosis
• Active infectious diseases
• Positive serology for HIV1 and 2, p24 Ag, HCV Abs, HBs Ag, HbC Abs, HTLV and II Abs, TPHA
• Need for perioperative antibiotic prophylaxi

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
heathly donors; patients who come as part of their routine care	Other: Reuse of surgical waste; Heathly donnors will be received in the plastic surgery department as part of routine care. They will be informed of the study and their surgical waste (adipose tissue) will be recovered specifically for this research.
CELLCORDES 2 Patient; Patient included in the clinical trial CELLCORDES 2	Other: Reuse of biological samples; Patients included in the cellcordes 2 trial who have given their consent for the re-use of their biological samples (Stromal Vascular Fraction) in other clinical research projects, and who have been informed of the cellcordes bio study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
collagene protein levels	The stromal vascular fraction of patient will be co-cultured with an in-vitro model of scarred vocal cord. Then, the levels of collagene will be quantified by western blot to measure the anti-fibrotic activity of SVF.	24 months
Actine alpha 2 (ACTA2) RNA levels	The stromal vascular fraction of patient will be co-cultured with an in-vitro model of scarred vocal cord. Then, the levels of ACTA2 will be quantified by RT-qPCR to measure the anti-fibrotic activity of SVF.	24 months
Alpha Smooth muscle actin (aSMA) protein levels	The stromal vascular fraction of patient will be co-cultured with an in-vitro model of scarred vocal cord. Then, the levels of aSMA will be quantified by western blot to measure the anti-fibrotic activity of SVF.	24 months
collagen type 1 alpha 1 chain (COL1A1) RNA levels	The stromal vascular fraction of patient will be co-cultured with an in-vitro model of scarred vocal cord. Then, the levels of COL1A1will be quantified by RT-qPCR to measure the anti-fibrotic activity of SVF.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
collagene protein levels	Cellular products obtained from adipose tissue obtained from healthy donnors will be co-cultured with an in-vitro model of scarred vocal cord. Then, the levels of collagen will be quantified by western blot to measure the anti-fibrotic activity of different cellular products.	24 months
Actine alpha 2 (ACTA2) levels	Cellular products obtained from adipose tissue of healthy donnors will be co-cultured with an in-vitro model of scarred vocal cord. Then, the levels of ACTA2 will be quantified by RT-qPCR to measure the anti-fibrotic activity of different cellular products.	24 months
Alpha Smooth muscle actin (aSMA) protein levels	Cellular products obtained from adipose tissue of healthy donnors will be co-cultured with an in-vitro model of scarred vocal cord. Then, the RNA levels of aSMA will be quantified by western blot to measure the anti-fibrotic activity of different cellular products	24 months
ollagen type 1 alpha 1 chain (COL1A1) RNA levels	Cellular products obtained from adipose tissue of healthy donnors will be co-cultured with an in-vitro model of scarred vocal cord. Then, the RNA levels of COL1A1 will be quantified by RT-qPCR to measure the anti-fibrotic activity of different cellular products.	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Collaborators: Aix Marseille Université
• Investigators: Principal Investigator: MATTEI Alexia, Doctor, Assistance Publique - Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix
• Other Study ID Numbers: RCAPHM24_0513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No