Dextromethorphan to Treat Patients With Voice Spasms

NCT00055549 | Completed Phase 1

• 2 other identifiers: 03011903-N-0119
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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. 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. ...

Conditions

Voice Disorders

Keywords

Dextromethorphan; Sensorimotor Modulation; Spasmodic Dysphonia; Muscular Tension Dysphonia; Voice Tremor; Lorazepam; Dysphonia; Macular Tension Dysphonia

Interventions

Dextromethorphan DRUG

Lorazepam DRUG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 9831047 BACKGROUND

• Ambalavanar 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.

  PMID: 11877499 BACKGROUND

• Aminoff 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.

  PMID: 650244 BACKGROUND

MeSH Terms

Conditions

Voice Disorders; Dysphonia

Interventions

Dextromethorphan; Lorazepam

Condition Hierarchy (Ancestors)

Laryngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 5, 2003
• First Posted: March 5, 2003
• Study Start: March 4, 2003
• Primary Completion: November 13, 2009
• Study Completion: November 13, 2009
• Last Updated: July 2, 2017

Record last verified: 2009-11-13

Locations

US (1)