Contact Ulcer of Vocal FoldsPhase 2NCT01678053
Efficacy Study of Botulinum Toxin (BOTOX) Injections to Treat Vocal Fold Granulomas
A Phase 2 study testing onabotulinumtoxinA and omeprazole (proton pump inhibitor) in people with Contact Ulcer of Vocal Folds and Granuloma of Vocal Cords, run by Phillip Song, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Contact Ulcer of Vocal Folds, Granuloma of Vocal Cords, Granuloma, Laryngeal
- What is being tested?
- onabotulinumtoxinA and omeprazole (proton pump inhibitor)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Jan 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults age 18 years old and older with vocal fold granulomas
- willing to attend all follow-up appointments
Who cannot join
- 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
Show all 10Show fewer
- vocal fold immobility
- pre-existing oropharyngeal swallowing problems
- history of radiation therapy
- history of aspiration pneumonia
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
Official title: 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.
Read the 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.
- Being tested
- onabotulinumtoxinA, omeprazole (proton pump inhibitor)
- Keywords
- Botulinum Toxins, Type A
- Medical subject headings
- Granuloma, Laryngeal, Granuloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
onabotulinumtoxinADrug
Also called BOTOX, Botulinum toxin A
Botulinum toxin A is injected into the larynx in order to treat vocal fold granulomas.
omeprazole (proton pump inhibitor)Drug
Also called omeprazole
Standard therapy of anti-reflux medications using omeprazole or equivalent PPI.
| Study group | Role | What they receive |
|---|---|---|
| PPI and BOTOX | Experimental | onabotulinumtoxinA (BOTOX), injection, 10 units, one time; omeprazole 40mg po bid (standard of care) for 3 months Receives: Drug: onabotulinumtoxinA; Drug: omeprazole (proton pump inhibitor) |
| Proton pump inhibitor only | Other | omeprazole 40mg po bid for 3 months(standard of care) Receives: Drug: omeprazole (proton pump inhibitor) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete resolution of vocal fold granuloma
Measured: 3 months
Secondary outcomes (1)
Voice Handicap Index score
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2012 (estimated)
- Study startSep 2012
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: Was not able to recruit patients for randomization.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Contact Ulcer of Vocal FoldsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phillip Song, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Phillip Song, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Phillip Song, M.D., Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01678053
- Sponsor's protocol ID
- 11-090H
- Status last verified
- Mar 2017
- First submitted
- 30 Aug 2012
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1097/00005537-199902000-00021.
PubMed 10890781Emami 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. doi: 10.1016/s0892-1997(99)80015-0.
PubMed 10622526Pham 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. doi: 10.1258/0022215042450788.
PubMed 15550184Nasri S, Sercarz JA, McAlpin T, Berke GS. Treatment of vocal fold granuloma using botulinum toxin type A. Laryngoscope. 1995 Jun;105(6):585-8. doi: 10.1288/00005537-199506000-00005.
PubMed 7769940Damrose EJ, Damrose JF. Botulinum toxin as adjunctive therapy in refractory laryngeal granuloma. J Laryngol Otol. 2008 Aug;122(8):824-8. doi: 10.1017/S0022215107000710. Epub 2007 Oct 2.
PubMed 17908354Ylitalo R, Lindestad PA. A retrospective study of contact granuloma. Laryngoscope. 1999 Mar;109(3):433-6. doi: 10.1097/00005537-199903000-00017.
PubMed 10089971
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial Comparing Proton Pump Inhibitor Therapy With and Without Interarytenoid Botulinum Toxin Injection for Vocal Fold Granuloma
- ClinicalTrials.gov ID
- NCT01678053
- Acronym / sponsor ID
- 11-090H
- Keywords
- Botulinum Toxins, Type A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Was not able to recruit patients for randomization.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Phillip Song, MDUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 3 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PPI and BOTOX | Experimental | Drug: onabotulinumtoxinA, Drug: omeprazole (proton pump inhibitor)onabotulinumtoxinA (BOTOX), injection, 10 units, one time; omeprazole 40mg po bid (standard of care) for 3 months |
| Proton pump inhibitor only | Other | Drug: omeprazole (proton pump inhibitor)omeprazole 40mg po bid for 3 months(standard of care) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- adults age 18 years old and older with vocal fold granulomas
- willing to attend all follow-up appointments
Key exclusion criteria (10 listed)
- pregnant females
- woman who are nursing
- minors and other patients unable to give informed consent
- patients taking Plavix
- patients with:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| onabotulinumtoxinAAlso: BOTOX, Botulinum toxin ABotulinum toxin A is injected into the larynx in order to treat vocal fold granulomas. | Drug | PPI and BOTOX |
| omeprazole (proton pump inhibitor)Also: omeprazoleStandard therapy of anti-reflux medications using omeprazole or equivalent PPI. | Drug | PPI and BOTOX, Proton pump inhibitor only |
Primary outcome
Complete resolution of vocal fold granuloma
Time frame: 3 months
1 secondary outcome
Voice Handicap Index score
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2017.
- Background: PubMed 10890781de 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. doi: 10.1097/00005537-199902000-00021.
- Background: PubMed 10622526Emami 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. doi: 10.1016/s0892-1997(99)80015-0.
- Background: PubMed 15550184Pham 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. doi: 10.1258/0022215042450788.
- Background: PubMed 7769940Nasri S, Sercarz JA, McAlpin T, Berke GS. Treatment of vocal fold granuloma using botulinum toxin type A. Laryngoscope. 1995 Jun;105(6):585-8. doi: 10.1288/00005537-199506000-00005.
- Background: PubMed 17908354Damrose EJ, Damrose JF. Botulinum toxin as adjunctive therapy in refractory laryngeal granuloma. J Laryngol Otol. 2008 Aug;122(8):824-8. doi: 10.1017/S0022215107000710. Epub 2007 Oct 2.
- Background: PubMed 10089971Ylitalo R, Lindestad PA. A retrospective study of contact granuloma. Laryngoscope. 1999 Mar;109(3):433-6. doi: 10.1097/00005537-199903000-00017.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Phillip Song, M.D. principal investigator
Massachusetts Eye and Ear Infirmary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing onabotulinumtoxinA and omeprazole (proton pump inhibitor) in people with Contact Ulcer of Vocal Folds and Granuloma of Vocal Cords, run by Phillip Song, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete resolution of vocal fold granuloma (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01678053, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2017.