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

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

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.

Study Overview

• Status: Completed
• Conditions: Dysphonia; Hoarseness; Vocal Fold Scar; Aphonia
• Intervention / Treatment: Biological: MSC-KI-PL-204

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm County
    • Stockholm, Stockholm County, Sweden, 11324
      • Karolinska Trial Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm: MSC administration to vocal fold scar; 1 single arm: Local injection of autologus MSC product (KI-MSC-PL-204) into scarred vocal fold (0,5-1 million cellls/Vocal fold, maximum 2 million cells if bilateral vocal fold scar)	Biological: MSC-KI-PL-204; Autologous MSC product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of treatment	Number of serious adverse events/ adverse events treatment and conseques	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of VF function by high speed laryngeal/stroboscopy recordings	Description: Assessment of VF function change from baseline to 1 year after treatment, as evaluated by an expert panel of high speed laryngeal/stroboscopy recordings. (Expert panel catagories: (Improved, unchanged, deteriorated)	from baseline to 1 year after treatment.
Assessment of subjective VHI change (points)	Assessment of patient´s subjective VHI (voice handicap index) ratings change (points)	changes from baseline to 1 year after treatement
Assessment of Phonation Threshold Pressure changes (cmH2O)	Measurements of phonation threshold pressure (PTP) changes from baseline to 1 year after treatment	changes from baseline to 1 year after treatment
Assessment of perceptual voice analysis changes (points)	Evaluation by an expert panel of perceptual voice parameters, changes from baseline to 1 year after treatment	changes from baseline to 1 year after treatment
Assessment of subjective VFI change (points)	Assessment of Vocal fatigue index (VFI) changes from baseline to 1 year after treatment	from baseline to 1 year after treatment
Assessment of maximum phonation time change (seconds)	Measurements of maximum phonation time change from baseline to 1 year after treatment	from baseline to 1 year after treatment

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Swedish Foundation for Strategic Research
• Investigators: Study Chair: Patric Scicluna, Clin Research Manager, Karolinska Trial Alliance

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): January 1, 2025
• Study Completion (Actual): January 1, 2025

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: MSC; dysphonia; Vocal fold scar
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Otorhinolaryngologic Diseases; Signs and Symptoms, Respiratory; Laryngeal Diseases; Voice Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Dysphonia; Hoarseness; Aphonia
• Other Study ID Numbers: 2019-06160 and 5.1-2019-92069

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No