Pilot Study of Stem Cell Treatment of Patients With Vocal Fold Scarring

Pilot Study of Patients With Severe Hoarseness and Vocal Fold Scarring Treated With Mesenchymal Stem Cells With and Without Hyaluronan Gel

This is a pilot-study of 16 selected Swedish patients which all have severe hoarseness or aphonia due to vocal fold scarring (from previous surgery, radiation therapy, inflammation or possibly hereditary). The patients are operated with phonomicrosurgical dissection of the scarred vocal folds, removal or scar tissue and injection of autologous mesenchymal stroma cells, aMSC (which were previously harvested from each patients´s bone marrow, purified, expanded and characterized according to standard procedure at the Center of Hematology and Regenerative Medicine Karolinska University Hospital Huddinge). 8 Patients is planned to be treated with a single injection of aMSC and 8 patients with injection of aMSC mixed with a carrier hyaluronan gel developed at Uppsala University Sweden and at the Karolinska Institute. The laryngeal status, vocal fold function, and voice function will be followed individually with an advanced battery of examinations performed before and up to 1 year postoperatively. Side effects and complications are noted and reported during surgery and following surgery at regular intervals during at least 1 year Since spring 2015 no new patients have been recruited and no treatments are given during 2016 or 2017. The monitoring authority was changed from Swedish National Board of Health to Swedish Medical Product Agency (MPA) in March/April 2016. Further inclusions and treatments are postponed until permission is granted from MPA to continue the study.

Study Overview

• Status: Completed
• Conditions: Improved Healing of Scarred Vocal Folds; Improved Vocal Fold Status; Improved Vocal Fold Function
• Intervention / Treatment: Biological: aMSC; Biological: aMSC+hyaluronan gel

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• severe hoarseness
• vocal fold scarring
• no active other treatment
• age above 18 years

Exclusion Criteria:

• active treatment of laryngeal disorder
• active inflammatory condition of the larynx
• diagnosed or suspicions of local malignancy

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: aMSC with and without hyaluronan gel; autologous mesenchymal stem cells (aMSC) injected into the vocal folds in 8 patients and aMSC mixed with hyaluronan gel in 8 patients	Biological: aMSC; aMSC injected into the vocal fold of the patient; Biological: aMSC+hyaluronan gel; aMSC+ hyaluronan gel is injected into the patients vocal fold

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved healing of scarred vocal folds	Laryngeal and general ear, nose, and throat status will be followed for each patient at least one year after primary treatment. This includes examination of signs of local (laryngeal) inflammatory reaction/defect healing, e.g. polyp or granuloma formation, inflammatory reaction after local aMSC injection It also includes repetitive examinations of vocal fold function and voice function including high speed examination of the vocal folds, acoustic voice analysis and phonation pressure measurements as well as subjective ratings by means of Voice handicap index scale	1 year postoperatively

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Karolinska Institutet; The Swedish Research Council; Laryngfonden

Publications and helpful links

General Publications

• Hertegard S, Nagubothu SR, Malmstrom E, LeBlanc K. Treatment of vocal fold scarring with autologous bone marrow-derived human mesenchymal stromal cells-first phase I/II human clinical study. Stem Cell Res Ther. 2020 Mar 20;11(1):128. doi: 10.1186/s13287-020-01632-8.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): February 24, 2020
• Study Completion (Actual): February 24, 2020

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (Estimate): November 11, 2013

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: mesenchymal stem cells; vocal fold scarring
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: 2010/1650 and 2014-51432