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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Massachusetts Eye and Ear Infirmary
Sponsor:
Information provided by (Responsible Party):
Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:
NCT01678053
First received: August 30, 2012
Last updated: September 11, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Contact Ulcer of Vocal Folds
Granuloma of Vocal Cords
Granuloma, Laryngeal
Granuloma
Drug: onabotulinumtoxinA
Drug: omeprazole (proton pump inhibitor)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial Comparing Proton Pump Inhibitor Therapy With and Without Interarytenoid Botulinum Toxin Injection for Vocal Fold Granuloma

Resource links provided by NLM:


Further study details as provided by Massachusetts Eye and Ear Infirmary:

Primary Outcome Measures:
  • Complete resolution of vocal fold granuloma [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Voice Handicap Index score [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: omeprazole
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 Name: omeprazole

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678053

Contacts
Contact: Matthew C Mori, M.D. 6507040753 matthew_mori@meei.harvard.edu
Contact: Phillip Song, M.D. 617-523-7900 phillip_song@meei.harvard.edu

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Contact: Mori       matthew_mori@meei.harvard.edu   
Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: Phillip Song, M.D. Massachusetts Eye and Ear Infirmary
  More Information

Publications:
Responsible Party: Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT01678053     History of Changes
Other Study ID Numbers: 11-090H
Study First Received: August 30, 2012
Last Updated: September 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts Eye and Ear Infirmary:
Botulinum Toxins, Type A

Additional relevant MeSH terms:
Pressure Ulcer
Granuloma
Granuloma, Laryngeal
Skin Ulcer
Skin Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Granuloma, Respiratory Tract
Respiratory Tract Diseases
Laryngeal Diseases
Respiratory Insufficiency
Respiration Disorders
Otorhinolaryngologic Diseases
Botulinum Toxins, Type A
Botulinum Toxins
Omeprazole
Proton Pump Inhibitors
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014