Voice DisordersPhase 1NCT00055549
Dextromethorphan to Treat Patients With Voice Spasms
A Phase 1 study testing Dextromethorphan and Lorazepam in people with Voice Disorders, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will examine how dextromethorphan, a drug that alters reflexes of the larynx (voice box), might change voice symptoms in people with voice disorders due to uncontrolled laryngeal muscle spasms. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Voice Disorders
- What is being tested?
- Dextromethorphan and Lorazepam
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2003to 13 Nov 2009
- Phase
- Phase 1
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Spasmodic Dysphonia will meet the following criteria:
- No structural abnormalities affecting the larynx such as vocal fold nodules, polyps, carcinoma, cysts, contact ulcers, inflammation (laryngitis).
- Symptoms of adductor or abductor spasmodic dysphonia present during speech and not apparent at rest,
- Symptoms of adductor or abductor spasmodic dysphonia less evident during whisper, singing or falsetto.
- Symptoms of adductor or abductor spasmodic dysphonia become worse with prolonged speaking, practice or anxiety.
- Reflexive and emotional aspects of voice function are unaffected, such as coughing and laughter or crying.
Show all 12Show fewer
- Patients with Muscular Tension Dysphonia will meet the following criteria:
- Increased phonatory muscle tension in the paralaryngeal and suprahyoid muscles on palpation,
- Constant elevation of the larynx in the neck during speech.
- A consistent hypertonic laryngeal posture for phonation, either an open posterior glottic chink between the arytenoid cartilages on phonation, an anterior-posterior squeeze (pin hole posture) or ventricular hyperadduction.
- A normally appearing larynx.
- Patients with vocal tremor will have tremor isolated to the larynx without noticeable tremor of the head and pharynx. Tremor of the vocal folds should be evident during a prolonged vowel and also noticeable in the larynx during connected speech containing vowels.
Who cannot join
- Subjects in all three groups will be without:
- Cardiac, pulmonary, neurological, psychiatric or speech and hearing problems as determined by medical history and examination by a physician and an EKG. Any patient with a history of airway obstruction will be excluded from the study.
- Reduction in the range of vocal fold movement during non-speech tasks such as whistling suggesting either paralysis or paresis, joint abnormality or neoplasm.
- No smokers or tobacco users will be included in the study.
- Exclude mucosal changes such as vocal nodules or polyps.
- Subjects with a history of a psychiatric disorder, under the care of a psychiatrist, or on medications for treatment of a psychiatric disorder will be excluded from study. Examples of psychiatric disorders to be excluded are: somatoform disorders, conversion disorders, currently under treatment for a major depression, or a history of schizophrenia or a bipolar disorder. However, a history of a previous episode of a minor reactive depression would not exclude a person from participation.
Show all 9Show fewer
- Subjects taking carbonic anhydrase inhibitors, cimetidine, hydrochlorthiazide, nicotine, quinidine, ranitidine, sodium or calcium bicarbonate and triamterene must either discontinue these medications or be excluded from study.
- Subjects with grade 2 or higher hepatic or renal dysfunction will be excluded from study.
- Pregnant women will be excluded from the study as it is not known if the study drugs are harmful to the fetus. If a woman becomes pregnant during the study, she will be removed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Effects of an NMDA-Receptor Antagonist in Idiopathic Voice Disorders
This study will examine how dextromethorphan, a drug that alters reflexes of the larynx (voice box), might change voice symptoms in people with voice disorders due to uncontrolled laryngeal muscle spasms. These include abductor spasmodic dysphonia (breathy voice breaks), adductor spasmodic dysphonia (vowel breaks), muscular tension dysphonia (tight strained voice), and vocal tremor (tremulous voice). Dextromethorphan-one of a group of drugs called NMDA antagonists-has been used for years in over-the-counter cough suppressant medicines. In animal studies, the drug has blocked one of the reflexes in the larynx that may be associated with spasms in the laryngeal muscles. This study will compare the effects of dextromethorphan, lorazepam (a valium-type drug), and a placebo (inactive substance) in patients with the four types of voice disorders described above.
Patients with spasmodic dysphonia, muscular tension dysphonia and vocal tremor may be eligible for this study. Individuals who smoke or use tobacco, who have vocal nodules or polyps, or who have a history of airway obstruction may not participate. Candidates will be screened with a medical history and physical examination, a questionnaire, voice recording (repeating sentences into a microphone), and nasolaryngoscopy (examination of the larynx with a tube advanced through the nose). For the nasolaryngoscopy, the inside of the nose is sprayed with a decongestant (to open the nasal passages) and possibly a local anesthetic. A small, flexible tube called a nasolaryngoscope is passed through the nose to look at the larynx during speech and other tasks, such as singing, whistling and prolonged vowels.
Read more
Participants will be admitted to the NIH Clinical Center for each of three visits, which will last from the afternoon of one day to late afternoon of the following day. At each visit, patients will complete a questionnaire, baseline speech recording, and a test for sedation level. They will take three pills-either dextromethorphan, lorazepam, or placebo-one every 6 hours. Vital signs will be checked every 6 hours and the level of sedation during waking hours will be monitored. One to three hours after taking the third pill, speech recording, questionnaire and test of sedation will be repeated to check for possible voice changes. Patients will be given a different pill at each visit.
...
Read the detailed description
Studies of spasmodic dysphonia (SD) have increasingly pointed to the possibility of a central sensori-motor control disorder. Sensori-motor processing has been found abnormal in both adductor and abductor spasmodic dysphonia based on reflex conditioning studies. These studies demonstrated an increased frequency of R2 muscle responses during rapid paired presentation of electrical stimuli to the superior laryngeal nerve in spasmodic dysphonia. Thus, uncontrolled R2 responses were hypothesized to be the basis for the uncontrolled muscle bursts in these patients. Selective suppression of late R2 laryngeal adductor responses by N-methyl-D-Aspartate (NMDA) blockade in cats was demonstrated by Ambalavanar et.al. In particular, dextromethorphan reduced the frequency of R2 responses from 95% to 25% (P = 0.015). Dextromethorphan is a widely used antitussive agent that has been in use for over 30 years. In a double-blind randomized crossover design, 3 groups of patients will receive be randomly assigned to one of 6 order cohorts. They will then receive either dextromethorphan at a 8 mg/kg/d dose divided in a Q6 hour dosing schedule with only 3 doses administered PO every 6 hours for 3 dosages, 04 mg/kg/d of lorazepam PO every 6 hours for 3 dosages or a placebo administrated in the same way during Phase A. After a minimum of a 1-week washout interval, the patients will be given either the other medication or placebo during Phase B and then the remaining medication or placebo during Phase C.
Our hypothesis is that dextromethorphan, an NMDA receptor blocker, will reduce voice breaks in spasmodic dysphonia to a greater degree than lorazepam, which has similar sedating side effects, but does not affect NMDA receptors with a different mechanism. On the other hand, patients with other idiopathic voice disorders, muscular tension dysphonia and vocal tremor, are hypothesized not to have a similar benefit from dextromethorphan. During the double-blind randomized cross-over study, three groups will be included, 10 patients with adductor or abductor spasmodic dysphonia, 10 with muscular tension dysphonia and 10 with vocal tremor. The results will determine if dextromethorphan has potential as a treatment option for patients with adductor or abductor SD.
- Conditions
- Voice Disorders
- Being tested
- Dextromethorphan, Lorazepam
- Keywords
- Dextromethorphan, Sensorimotor Modulation, Spasmodic Dysphonia, Muscular Tension Dysphonia, Voice Tremor, Lorazepam, Dysphonia, Macular Tension Dysphonia
- Medical subject headings
- Voice Disorders, Dysphonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextromethorphanDrug
LorazepamDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2003 (estimated)
- Study start4 Mar 2003
- Primary completion13 Nov 2009
- Study completion13 Nov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Voice DisordersStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Enrolment
- 65 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00055549
- Sponsor's protocol ID
- 030119
- Other IDs
- 03-N-0119
- Status last verified
- 13 Nov 2009
- First submitted
- 5 Mar 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Ambalavanar R, Ludlow CL, Wenthold RJ, Tanaka Y, Damirjian M, Petralia RS. Glutamate receptor subunits in the nucleus of the tractus solitarius and other regions of the medulla oblongata in the cat. J Comp Neurol. 1998 Dec 7;402(1):75-92.
PubMed 9831047Ambalavanar R, Purcell L, Miranda M, Evans F, Ludlow CL. Selective suppression of late laryngeal adductor responses by N-methyl-D-aspartate receptor blockade in the cat. J Neurophysiol. 2002 Mar;87(3):1252-62. doi: 10.1152/jn.00595.2001.
PubMed 11877499Aminoff MJ, Dedo HH, Izdebski K. Clinical aspects of spasmodic dysphonia. J Neurol Neurosurg Psychiatry. 1978 Apr;41(4):361-5. doi: 10.1136/jnnp.41.4.361.
PubMed 650244
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of an NMDA-Receptor Antagonist in Idiopathic Voice Disorders
- ClinicalTrials.gov ID
- NCT00055549
- Acronym / sponsor ID
- 030119
- Conditions
- Voice Disorders
- Keywords
- Dextromethorphan, Sensorimotor Modulation, Spasmodic Dysphonia, Muscular Tension Dysphonia, Voice Tremor, Lorazepam, Dysphonia, Macular Tension Dysphonia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 4 Mar 2003
- Primary completion
- 13 Nov 2009 (actual)
- Study completion
- 13 Nov 2009 (actual)
- First posted
- 5 Mar 2003 (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.
This study will examine how dextromethorphan, a drug that alters reflexes of the larynx (voice box), might change voice symptoms in people with voice disorders due to uncontrolled laryngeal muscle spasms. These include abductor spasmodic dysphonia (breathy voice breaks), adductor spasmodic dysphonia (vowel breaks), muscular tension dysphonia (tight strained voice), and vocal tremor (tremulous voice). Dextromethorphan-one of a group of drugs called NMDA antagonists-has been used for years in over-the-counter cough suppressant medicines. In animal studies, the drug has blocked one of the reflexes in the larynx that may be associated with spasms in the laryngeal muscles. This study will compare the effects of dextromethorphan, lorazepam (a valium-type drug), and a placebo (inactive substance) in patients with the four types of voice disorders described above.
Patients with spasmodic dysphonia, muscular tension dysphonia and vocal tremor may be eligible for this study. Individuals who smoke or use tobacco, who have vocal nodules or polyps, or who have a history of airway obstruction may not participate. Candidates will be screened with a medical history and physical examination, a questionnaire, voice recording (repeating sentences into a microphone), and nasolaryngoscopy (examination of the larynx with a tube advanced through the nose). For the nasolaryngoscopy, the inside of the nose is sprayed with a decongestant (to open the nasal passages) and possibly a local anesthetic. A small, flexible tube called a nasolaryngoscope is passed through the nose to look at the larynx during speech and other tasks, such as singing, whistling and prolonged vowels.
Participants will be admitted to the NIH Clinical Center for each of three visits, which will last from the afternoon of one day to late afternoon of the following day. At each visit, patients will complete a questionnaire, baseline speech recording, and a test for sedation level. They will take three pills-either dextromethorphan, lorazepam, or placebo-one every 6 hours. Vital signs will be checked every 6 hours and the level of sedation during waking hours will be monitored. One to three hours after taking the third pill, speech recording, questionnaire and test of sedation will be repeated to check for possible voice changes. Patients will be given a different pill at each visit.
...
Detailed description
Studies of spasmodic dysphonia (SD) have increasingly pointed to the possibility of a central sensori-motor control disorder. Sensori-motor processing has been found abnormal in both adductor and abductor spasmodic dysphonia based on reflex conditioning studies. These studies demonstrated an increased frequency of R2 muscle responses during rapid paired presentation of electrical stimuli to the superior laryngeal nerve in spasmodic dysphonia. Thus, uncontrolled R2 responses were hypothesized to be the basis for the uncontrolled muscle bursts in these patients. Selective suppression of late R2 laryngeal adductor responses by N-methyl-D-Aspartate (NMDA) blockade in cats was demonstrated by Ambalavanar et.al. In particular, dextromethorphan reduced the frequency of R2 responses from 95% to 25% (P = 0.015). Dextromethorphan is a widely used antitussive agent that has been in use for over 30 years. In a double-blind randomized crossover design, 3 groups of patients will receive be randomly assigned to one of 6 order cohorts. They will then receive either dextromethorphan at a 8 mg/kg/d dose divided in a Q6 hour dosing schedule with only 3 doses administered PO every 6 hours for 3 dosages, 04 mg/kg/d of lorazepam PO every 6 hours for 3 dosages or a placebo administrated in the same way during Phase A. After a minimum of a 1-week washout interval, the patients will be given either the other medication or placebo during Phase B and then the remaining medication or placebo during Phase C.
Our hypothesis is that dextromethorphan, an NMDA receptor blocker, will reduce voice breaks in spasmodic dysphonia to a greater degree than lorazepam, which has similar sedating side effects, but does not affect NMDA receptors with a different mechanism. On the other hand, patients with other idiopathic voice disorders, muscular tension dysphonia and vocal tremor, are hypothesized not to have a similar benefit from dextromethorphan. During the double-blind randomized cross-over study, three groups will be included, 10 patients with adductor or abductor spasmodic dysphonia, 10 with muscular tension dysphonia and 10 with vocal tremor. The results will determine if dextromethorphan has potential as a treatment option for patients with adductor or abductor SD.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- No structural abnormalities affecting the larynx such as vocal fold nodules, polyps, carcinoma, cysts, contact ulcers, inflammation (laryngitis).
- Symptoms of adductor or abductor spasmodic dysphonia present during speech and not apparent at rest,
- Symptoms of adductor or abductor spasmodic dysphonia less evident during whisper, singing or falsetto.
- Symptoms of adductor or abductor spasmodic dysphonia become worse with prolonged speaking, practice or anxiety.
- Reflexive and emotional aspects of voice function are unaffected, such as coughing and laughter or crying.
Key exclusion criteria (9 listed)
- Cardiac, pulmonary, neurological, psychiatric or speech and hearing problems as determined by medical history and examination by a physician and an EKG. Any patient with a history of airway obstruction will be excluded from the study.
- Reduction in the range of vocal fold movement during non-speech tasks such as whistling suggesting either paralysis or paresis, joint abnormality or neoplasm.
- No smokers or tobacco users will be included in the study.
- Exclude mucosal changes such as vocal nodules or polyps.
- Subjects with a history of a psychiatric disorder, under the care of a psychiatrist, or on medications for treatment of a psychiatric disorder will be excluded from study. Examples of psychiatric disorders to be excluded are: somatoform disorders, conversion disorders, currently under treatment for a major depression, or a history of schizophrenia or a bipolar disorder. However, a history of a previous episode of a minor reactive depression would not exclude a person from participation.
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 |
|---|---|---|
| Dextromethorphan | Drug | – |
| Lorazepam | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 9831047Ambalavanar R, Ludlow CL, Wenthold RJ, Tanaka Y, Damirjian M, Petralia RS. Glutamate receptor subunits in the nucleus of the tractus solitarius and other regions of the medulla oblongata in the cat. J Comp Neurol. 1998 Dec 7;402(1):75-92.
- Background: PubMed 11877499Ambalavanar R, Purcell L, Miranda M, Evans F, Ludlow CL. Selective suppression of late laryngeal adductor responses by N-methyl-D-aspartate receptor blockade in the cat. J Neurophysiol. 2002 Mar;87(3):1252-62. doi: 10.1152/jn.00595.2001.
- Background: PubMed 650244Aminoff MJ, Dedo HH, Izdebski K. Clinical aspects of spasmodic dysphonia. J Neurol Neurosurg Psychiatry. 1978 Apr;41(4):361-5. doi: 10.1136/jnnp.41.4.361.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dextromethorphan and Lorazepam in people with Voice Disorders, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 12 inclusion and 9 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: finished, as of the sponsor's last update on 2 Jul 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00055549, which also lists 3 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 2 Jul 2017.