Efficacy Study of Botulinum Toxin (BOTOX) Injections to Treat Vocal Fold Granulomas

March 24, 2017 updated by: Phillip Song, MD

A Randomized Controlled Trial Comparing Proton Pump Inhibitor Therapy With and Without Interarytenoid Botulinum Toxin Injection for Vocal Fold Granuloma

Vocal process granulomas are inflammatory masses caused in part by vocal trauma that arise in the posterior aspect of the vocal folds and result in throat pain, difficulty swallowing, hoarseness, and globus sensation. Antireflux therapy treats most granulomas, but many are recalcitrant to this therapy or take months to years to resolve. Botulinum toxin injection into the thyroarytenoid muscle has been effectively employed for recalcitrant granuloma, but causes significant voice loss, occasional difficulty swallowing and, in our clinical experience, is associated with significant recurrence. The investigators propose injecting another muscle in the larynx called the interarytenoid muscle with botulinum toxin type A to maintain the benefit of injection with less loss of voice. The investigators have shown the effectiveness of this treatment in a small, retrospective analysis.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Vocal fold granulomas may be due to reflux, voice trauma, intubation, multiple or unknown etiologies. Regimens of voice therapy and anti-reflux medications have show resolution rates varying from 38% to 100%, with recurrence rates of 15-20%, and up to 50-92% in surgical-operated on recalcitrant granulomas. Nasri and colleagues first proposed thyroarytenoid botulinum toxin type A (BOTOX) injections for vocal fold granulomas with success. They posited that the chemically paralyzed muscle would result in limited contact at the site of the granuloma, allowing for healing. Damrose and Damrose further showed that thyroarytenoid BOTOX injections were effective in treating recalcitrant vocal fold granulomas. Both of the above groups noted hoarseness as an expected side effect. Pham and colleagues showed complete resolution of granulomas in 2-8 weeks after treatment with thyroarytenoid BOTOX injections. This was compared to mean granuloma resolution of 5.7 months proton pump inhibitor therapy alone. The investigators reviewed eight patients treated for recalcitrant vocal fold granuloma at Mass Eye and Ear with interarytenoid BOTOX injections and found no serious adverse effects and complete response in seven cases. The investigators now seek to compare interarytenoid BOTOX injections to standard anti-reflux therapy alone to see if the addition of IA Botox injections improves response rates at 3 months. The investigators chose this timeframe since 86% of granulomas treated in our retrospective study had resolved 3 months after initiation of treatment compared to 25% of granulomas treated with medical management.

The investigators will not include a Thyroarytenoid injection arm in this study as this technique has not been useful in our clinical experience.

For those who consent, a Voice Handicap Index survey (6 - see attached) will be completed. Participants will then be randomized to undergo only medical therapy with omeprazole (40mg by mouth twice daily ) or an interarytenoid BOTOX injection followed by the same reflux regimen. Randomization will be performed by the Tufts online randomization plan, which may be found at: http://www.tufts.edu/~gdallal/PLANDOC.HTM. This program generates a random order in which participants will be enrolled in either of the two arms of the study.

The injection will consist of 10 units of botulinum toxin injected into the interarytenoid muscle under fiberoptic visualization. All participants will remain on the PPI therapy for the duration of the study. Participants will receive prescriptions for PPI medication from the attending Laryngologist and participants will then be responsible for acquiring and taking their medications.

Injections will be performed per standard MEEI Laryngology protocol for interarytenoid BOTOX injection. Participants will then be evaluated at 1.5 months, 3 months and 6 months with fiberoptic examination as well as Voice Handicap Index & Reflux Symptom Index. Participants in the medication only arm who continue to have a granuloma at 3 months will receive a BOTOX injection. They will be re-evaluated 3 months after the injection. Examinations will be recorded and reviewed by blinded reviewers.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • adults age 18 years old and older with vocal fold granulomas
  • willing to attend all follow-up appointments

Exclusion Criteria:

  • pregnant females
  • woman who are nursing
  • minors and other patients unable to give informed consent
  • patients taking Plavix
  • patients with:
  • impaired laryngeal motion as the result of neurological impairment
  • vocal fold immobility
  • pre-existing oropharyngeal swallowing problems
  • history of radiation therapy
  • history of aspiration pneumonia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PPI and BOTOX
onabotulinumtoxinA (BOTOX), injection, 10 units, one time; omeprazole 40mg po bid (standard of care) for 3 months
Drug: onabotulinumtoxinA
Botulinum toxin A is injected into the larynx in order to treat vocal fold granulomas.
Other Names:
  • BOTOX
  • Botulinum toxin A
Drug: omeprazole (proton pump inhibitor)
Standard therapy of anti-reflux medications using omeprazole or equivalent PPI.
Other Names:
  • omeprazole
Other: Proton pump inhibitor only
omeprazole 40mg po bid for 3 months(standard of care)
Drug: omeprazole (proton pump inhibitor)
Standard therapy of anti-reflux medications using omeprazole or equivalent PPI.
Other Names:
  • omeprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete resolution of vocal fold granuloma
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Voice Handicap Index score
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phillip Song, MD

Investigators

  • Principal Investigator: Phillip Song, M.D., Massachusetts Eye and Ear Infirmary

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

August 30, 2012

First Submitted That Met QC Criteria

August 31, 2012

First Posted (Estimate)

September 3, 2012

Study Record Updates

Last Update Posted (Actual)

March 28, 2017

Last Update Submitted That Met QC Criteria

March 24, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11-090H

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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