A Study of Local Administration of Autologous Mesenchymal Stromal Cells in Dysphonic Patients With Vocal Fold Scarring

Dysphonia Clinical Trial

Official title:

An Open Phase I/II Study in Patients With Dysphonia and Vocal Fold Scarring to Evaluate Safety, Tolerability and Vocal Function After Surgery With Local Administration of Autologous Mesenchymal Stromal Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04290182
• Other study ID #: 2019-06160 and 5.1-2019-92069
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2020
• Est. completion date: June 2023

Study information

• Verified date: February 2020
• Source: Karolinska University Hospital
• Contact: Stellan Hertegård, Adj Professor. MD PhD
• Phone: +468585850000
• Email: Stellan.Hertegard[@]sll.se, Stellan.Hertegard[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall aim of the project is to develop a new method for treatment of untreatable severe hoarseness due to vocal fold scarring by local injection of autologous mesenchymal stromal cells (MSC). At present there is no lasting effective treatment for this condition which results in personal suffering, and often extended sick leave, change of work or unemployement for the patients.

Based on the previous results the investigators expect the autologous MSC product KI-MSC-PL-204 to be a new effective treatment without side effects for many patients with severe hoarseness or aphonia due to vocal fold scarring.

Description:

The general aim of the project is to develop a treatment for severe hoarseness due to vocal fold (VF) scarring. Vocal fold scarring can be caused by tumor surgery, radiotherapy, severe inflammation or is early acquired (sulcus vocalis with scar) and results in stiff vocal folds with decreased vibratory capacity and severe deterioration or total loss of voice (aphonia). There is no lasting effective treatment. Bone marrow derived mesenchymal stem cells (MSC) are immunomodulatory, decrease inflammation and improve endogenous healing. After receiving ethical permission the investigators have since 2012 treated 16 patients with manifest vocal fold scarring and severe hoarseness by scar resection and local injection of autologous bone marrow MSC to restore speech. This project was the first in the world to study the effects of MSC treatment of vocal fold scarring in humans. Analysis was made before and up to 12 months post operatively with voice recordings, examination with high speed camera and elasticity measurements of the vocal folds with novel technology. No side effects were found for any patient and for two thirds of the patients with 12 months follow-up the vocal fold function improved and no patient deteriorated.

While cell therapy with autologous MSC was classified according to the Tissue Legislation before 2015, it is now regarded as drug treatment. In accordance with this legislation, the MSC production is now full scale GMP. The investigators have recently received permissions from Swedish Medical Product Agency (DNr 5.1-2019-92069) and from the Regional ethic committee (Drn 2019-06160) for an open Phase I/Il study in patients with severe dysphonia and vocal fold scarring to evaluate safety, tolerability and vocal function after surgery with local administration of autologous mesenchymal stromal cell product KI-MSC-PL-204 as an extended study on 15 patients.

MSC may in the future be used to treat patients with severe hoarseness due to scarring, as well as other damages in the airways.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 2023
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients between 18-65 years with VF scarring and severe voice problems, such as permanent severe hoarseness, complete aphonia or severe voice strain during speech (>1 year) where other treatments have proven ineffective and no alternative treatment is possible.

• No alternative treatment ongoing or planned (phonosurgery with augmentation implantation, voice therapy or other medical treatment).

Exclusion Criteria:

• Active treatment of laryngeal disorder, inflammatory condition of the larynx, or laryngeal/VF papilloma.

• Diagnosed or suspicion of local malignancy or other malignancies, Disease-free period of >5 years after malignant disease (>10 years for local laryngeal cancer).

• Smokers.

• Large scar defects.

• Pregnant or nursing (lactating) women.

• Serological evidence of infection with HIV, HBV, HCV, HTLV and/or syphilis.

• Active ongoing local or systemic infections.

• Ongoing immune suppressive treatment.

Related Conditions & MeSH terms

• Aphonia
• Dysphonia
• Hoarseness
• Vocal Fold; Scar

Intervention

Biological:
• MSC-KI-PL-204
Autologous MSC product

Locations

Country	Name	City	State
Sweden	Karolinska Trial Alliance	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska University Hospital	Swedish Foundation for Strategic Research

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of treatment	Number of serious adverse events or adverse events	1 year
Primary	Assessment of VF function	Assessment of VF function, as evaluated by high speed laryngeal/stroboscopy recordings, phonation threshold pressure and acoustic and perceptual voice analysis.	1 year
Primary	Assessment of subjective voice ratings	Assessment of patient´s subjective VHI ratings	1 year
Primary	Assessment of tissue metabolism and healing	Assessment of VF healing with PET-CT scans	1 year