A Phase 2 Trial of Deep Brain Stimulation for Spasmodic Dysphonia

NCT04938154 | Unknown Phase 2 DMC

• 1 other identifier: H21-00728
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Spasmodic Dysphonia (SD) is a focal, action-specific movement disorder with prominent effects on speech (1, 2). Patients with SD lose their ability to speak normally due to involuntary contractions of their laryngeal muscles. As a result, SD tremendously affects an individual's quality of life by limiting their ability to communicate effectively. The current standard of care for SD involves botulinum toxin (BTX) injections into the laryngeal muscles. BTX causes a weakness in the injected muscles thereby lessening the spasms (3). The primary neurological problem is not changed but weakening the muscles temporarily diminishes the symptoms. However, BTX therapy is associated with several limitations (3, 4). First, the clinical effect produced by BTX is temporary and repeated injections are required approximately every 3 months. Second, there is a delay in the onset of benefits provided by BTX injections; this delay results in a sinusoidal symptom curve where SD is optimally controlled for only a portion of each treatment cycle and patients' spasms return prior to the next injection cycle. Furthermore, the injections can be very painful and some patients develop antibodies to BTX (3, 4). Oral medications used in dystonia, such as anticholinergics, benzodiazepines, and baclofen, provide minimal relief and have numerous side effects at the doses required to influence a patient's voice. Thus, on basis of these limitations, we set out to explore new and innovative strategies to treat SD and provide patients with long-term benefit. Deep Brain Stimulation (DBS) is a neurosurgical procedure that involves the implantation of electrodes to deliver electrical stimuli to specific brain regions. It is the gold-standard surgical treatment for other movement disorders such as Parkinson's disease and generalized dystonia. During a DBS procedure, an electrode is inserted very precisely into the brain and is linked to a pacemaker implanted under the skin of the chest or abdominal wall. When the pacemaker is switched on, a very small electric current passes into the brain, blocking the damaging signals that cause the condition.

Conditions

Spasmodic Dysphonia

Keywords

Deep Brain Stimulation

Outcome Measures

Primary Outcomes (1)

• Patient Voice-Related Quality of Life as assessed by the Voice-Related Quality of Life questionnaire.

  The primary endpoint will be the Voice-Related Quality of Life (V-RQOL) reported by the patients after three months of blinded DBS-ON or DBS-OFF

  6 months

Study Arms (2)

DBS On

EXPERIMENTAL

Device: DBS ON

DBS Off

SHAM COMPARATOR

Device: DBS OFF

Interventions

DBS ON DEVICE

The DBS system will be turned on and the patient will be left on their best setting for 3 months.

DBS On

DBS OFF DEVICE

The DBS system will be turned off, and will be left off for 3 months.

DBS Off

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of spasmodic dysphonia (evaluated by 2 centres - one team in Vancouver and the other team in Indiana)
• Patient is receiving Botox treatments

You may not qualify if:

• Patients who have muscle tension dysphonia or vocal tremor
• Patients who have had laryngeal denervation surgery
• Patients who have intracranial pathology
• Patients who have a neurodegenerative disease
• Patients with bleeding diathesis
• Patients with mild symptoms
• Patients who have any of the following MRI contraindications:
• Patients with a cardiac pacemaker or defibrillator
• Patients who have an insulin or infusion pump
• Patients who have a cochlear, otological, or ear implant
• Patients who have any implant held in place by a magnet
• Patients who have any tissue expanders
• Patients who have an implanted catheter, clamps, clips, valves, or other metal
• Patients who have any tattoos or permanent makeup above shoulders
• Patients who have any shrapnel or metal fragments

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Leslie and Gordon Diamond Health Care Center

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (14)

• Jankovic J, Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry. 1990 Aug;53(8):633-9. doi: 10.1136/jnnp.53.8.633.

  PMID: 2213039 BACKGROUND

• White LJ, Klein AM, Hapner ER, Delgaudio JM, Hanfelt JJ, Jinnah HA, Johns MM 3rd. Coprevalence of tremor with spasmodic dysphonia: a case-control study. Laryngoscope. 2011 Aug;121(8):1752-5. doi: 10.1002/lary.21872.

  PMID: 21792965 BACKGROUND

• Bielamowicz S, Stager SV, Badillo A, Godlewski A. Unilateral versus bilateral injections of botulinum toxin in patients with adductor spasmodic dysphonia. J Voice. 2002 Mar;16(1):117-23. doi: 10.1016/s0892-1997(02)00080-2.

  PMID: 12002878 BACKGROUND

• Zwirner P, Murry T, Swenson M, Woodson GE. Effects of botulinum toxin therapy in patients with adductor spasmodic dysphonia: acoustic, aerodynamic, and videoendoscopic findings. Laryngoscope. 1992 Apr;102(4):400-6. doi: 10.1288/00005537-199204000-00006.

  PMID: 1556889 BACKGROUND

• Honey CR, Kruger MT, Almeida T, Rammage LA, Tamber MS, Morrison MD, Poologaindran A, Hu A. Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial. Neurosurgery. 2021 Jun 15;89(1):45-52. doi: 10.1093/neuros/nyab095.

  PMID: 33862624 BACKGROUND

• Patel RR, Liu L, Galatsanos N, Bless DM. Differential vibratory characteristics of adductor spasmodic dysphonia and muscle tension dysphonia on high-speed digital imaging. Ann Otol Rhinol Laryngol. 2011 Jan;120(1):21-32. doi: 10.1177/000348941112000104.

  PMID: 21370677 BACKGROUND

• Poburka BJ, Patel RR, Bless DM. Voice-Vibratory Assessment With Laryngeal Imaging (VALI) Form: Reliability of Rating Stroboscopy and High-speed Videoendoscopy. J Voice. 2017 Jul;31(4):513.e1-513.e14. doi: 10.1016/j.jvoice.2016.12.003. Epub 2016 Dec 28.

  PMID: 28040342 BACKGROUND

• Patel RR, Awan SN, Barkmeier-Kraemer J, Courey M, Deliyski D, Eadie T, Paul D, Svec JG, Hillman R. Recommended Protocols for Instrumental Assessment of Voice: American Speech-Language-Hearing Association Expert Panel to Develop a Protocol for Instrumental Assessment of Vocal Function. Am J Speech Lang Pathol. 2018 Aug 6;27(3):887-905. doi: 10.1044/2018_AJSLP-17-0009.

  PMID: 29955816 BACKGROUND

• Roy N, Mauszycki SC, Merrill RM, Gouse M, Smith ME. Toward improved differential diagnosis of adductor spasmodic dysphonia and muscle tension dysphonia. Folia Phoniatr Logop. 2007;59(2):83-90. doi: 10.1159/000098341.

  PMID: 17337898 BACKGROUND

• Parker LA, Kunduk M, Fink DS, McWhorter A. Reliability of High-speed Videoendoscopic Ratings of Essential Voice Tremor and Adductor Spasmodic Dysphonia. J Voice. 2019 Jan;33(1):16-26. doi: 10.1016/j.jvoice.2017.10.009. Epub 2017 Dec 13.

  PMID: 29246397 BACKGROUND

• Yiu Y, Baylor CR, Bamer AM, Shelly S, Klein AM, Garrett CG, Pitman MJ. Validation of the Communicative Participation Item Bank as an Outcome Measure for Spasmodic Dysphonia. Laryngoscope. 2021 Apr;131(4):859-864. doi: 10.1002/lary.28897. Epub 2020 Jul 25.

  PMID: 32710809 BACKGROUND

• Simonyan K, Tovar-Moll F, Ostuni J, Hallett M, Kalasinsky VF, Lewin-Smith MR, Rushing EJ, Vortmeyer AO, Ludlow CL. Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. Brain. 2008 Feb;131(Pt 2):447-59. doi: 10.1093/brain/awm303. Epub 2007 Dec 14.

  PMID: 18083751 BACKGROUND

• Burgel U, Madler B, Honey CR, Thron A, Gilsbach J, Coenen VA. Fiber tracking with distinct software tools results in a clear diversity in anatomical fiber tract portrayal. Cent Eur Neurosurg. 2009 Feb;70(1):27-35. doi: 10.1055/s-0028-1087212. Epub 2009 Feb 3.

  PMID: 19191204 BACKGROUND

• Coenen VA, Jenkner C, Honey CR, Madler B. Electrophysiologic Validation of Diffusion Tensor Imaging Tractography during Deep Brain Stimulation Surgery. AJNR Am J Neuroradiol. 2016 Aug;37(8):1470-8. doi: 10.3174/ajnr.A4753. Epub 2016 Mar 31.

  PMID: 27032969 BACKGROUND

MeSH Terms

Conditions

Dysphonia

Condition Hierarchy (Ancestors)

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

Study Officials

• Christopher R Honey, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle Pietramala, BSc

CONTACT

604-875-4111; danielle.pietram@ubc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurosurgery

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: June 24, 2021
• Study Start: January 30, 2023
• Primary Completion: September 30, 2025
• Study Completion: December 30, 2025
• Last Updated: November 1, 2022

Record last verified: 2022-10

Locations

CA (1)