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

• ClinicalTrials.gov Identifier: NCT01678053
• Recruitment Status: Withdrawn
• First Posted: September 3, 2012
• Last Update Posted: March 28, 2017
• Sponsor: Phillip Song, MD
• Information provided by (Responsible Party): Phillip Song, MD, Massachusetts Eye and Ear Infirmary

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Contact Ulcer of Vocal Folds; Granuloma of Vocal Cords; Granuloma, Laryngeal; Granuloma	Drug: onabotulinumtoxinA; Drug: omeprazole (proton pump inhibitor)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: September 2012
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: January 2015

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

1. Complete resolution of vocal fold granuloma [ Time Frame: 3 months ]

Secondary Outcome Measures :

1. Voice Handicap Index score [ Time Frame: 3 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Massachusetts

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Phillip Song, MD

Investigators

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

More Information

Publications:

de Lima Pontes PA, De Biase NG, Gadelha EC. Clinical evolution of laryngeal granulomas: treatment and prognosis. Laryngoscope. 1999 Feb;109(2 Pt 1):289-94.

Emami AJ, Morrison M, Rammage L, Bosch D. Treatment of laryngeal contact ulcers and granulomas: a 12-year retrospective analysis. J Voice. 1999 Dec;13(4):612-7.

Pham J, Yin S, Morgan M, Stucker F, Nathan CO. Botulinum toxin: helpful adjunct to early resolution of laryngeal granulomas. J Laryngol Otol. 2004 Oct;118(10):781-5.

Nasri S, Sercarz JA, McAlpin T, Berke GS. Treatment of vocal fold granuloma using botulinum toxin type A. Laryngoscope. 1995 Jun;105(6):585-8.

Damrose EJ, Damrose JF. Botulinum toxin as adjunctive therapy in refractory laryngeal granuloma. J Laryngol Otol. 2008 Aug;122(8):824-8. Epub 2007 Oct 2.

Ylitalo R, Lindestad PA. A retrospective study of contact granuloma. Laryngoscope. 1999 Mar;109(3):433-6.

• Responsible Party: Phillip Song, MD, Otolaryngologist, Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT01678053
• Other Study ID Numbers: 11-090H
• First Posted: September 3, 2012
• Last Update Posted: March 28, 2017
• Last Verified: March 2017

Keywords provided by Phillip Song, MD, Massachusetts Eye and Ear Infirmary:

Botulinum Toxins, Type A

Additional relevant MeSH terms:

Granuloma, Laryngeal; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Pathologic Processes; Granuloma, Respiratory Tract; Respiratory Tract Diseases; Laryngeal Diseases; Respiratory Insufficiency; Respiration Disorders; Otorhinolaryngologic Diseases; Omeprazole; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Proton Pump Inhibitors; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Anti-Ulcer Agents; Gastrointestinal Agents; Enzyme Inhibitors; Neuromuscular Agents; Peripheral Nervous System Agents