Thalamic Deep Brain Stimulation for Spasmodic Dysphonia- DEBUSSY Trial

• Sponsor: University of British Columbia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02558634
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 50
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Laryngeal Dystonia (LD), also commonly referred to as spasmodic dysphonia, is a neurological voice disorder characterized by involuntary dystonic contractions of the laryngeal muscles. Current treatments such as botox and voice therapy only provide temporary relief and thus, the investigators are exploring new strategies to provide long-term, sustained improvement.

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 standard surgical treatment for many other movement disorders such as Parkinson's disease, essential tremor, and primary dystonia. This trial has been designed to test the hypothesis that DBS can improve the vocal dysfunction of LD.

Condition or Disease	Intervention/Treatment	Phase
Spasmodic Dysphonia; Laryngeal Dystonia; Deep Brain Stimulation	Device: VIM Thalamic Deep Brain Stimulation ON; Device: VIM Thalamic Deep Brain Stimulation OFF	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Prospective, Randomized, Double-Blinded, Sham-Controlled Trial
• Actual Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DBS-on Ventral intermediate Nucleus (VIM) Thalamic DBS on DBS system includes: Implantable Pulse Generator (IPG) DBS Lead DBS Lead Extension Kit	Device: VIM Thalamic Deep Brain Stimulation ON
Sham Comparator: DBS-off (sham-stimulation) Ventral intermediate Nucleus (VIM) Thalamic DBS off DBS system includes: Implantable Pulse Generator (IPG) DBS Lead DBS Lead Extension Kit	Device: VIM Thalamic Deep Brain Stimulation OFF

Outcome Measures

Primary Outcome Measures

1. Unified Spasmodic Dysphonia Rating Scale (USDRS) [After the first 6 months, the participants completed the USDRS twice (once per crossover).]

   Assessments of spasmodic dysphonia using a standardized spasmodic dysphonia rating scale were done pre-operatively, blinded DBS ON, blinded DBS OFF, and open DBS ON. Voice recording taken of each patient reading standardized sentences were blinded and evaluated by two speech language pathologists. The scale ranges from 0-7, with lower scores being better and higher scores being worse.

2. Voice-Related Quality of Life [After the first 6 months, the participants completed the V-RQoL twice (once per crossover).]

   Double-blinded assessments of voice-related quality of life with DBS ON/OFF were conducted using the V-RQoL for Spasmodic Dysphonia. The V-RQoL is a questionnaire that measures a patient's voice related quality of life. The scale ranges from 0-50, with higher scores representing a lower quality of life with respect to voice.

Secondary Outcome Measures

1. Beck's Depression Inventory Scale [All participants completed the BDI-II once pre-operatively and once 1 year post-operatively (after the 6-month open unblinded phase).]

   Beck's Depression Inventory Scale (BDI-II) was used in this study to evaluate the mood of the patients both pre-operatively and at the end of the one-year study. All 6 patients completed the BDI-II, which is a scale that identifies symptoms and attitudes associated with depression, and evaluates the presence and severity of depression. The BDI-II ranges from 0-63. Scores ranging from 0-10 are considered to be absent or minimal depression, 10-18 indicate mild to moderate depression, 19-29 indicate moderate depression, and 30-63 indicate severe depression.

2. Montreal Cognitive Assessment Scale (MoCA) [All participants completed the MoCA once pre-operatively and once 1 year post-operatively (after the 6-month open unblinded phase).]

   The MoCA was used to analyze the cognitive ability of the patients. It was first evaluated pre-operatively and again evaluated at the end of the one-year study. The MoCA scale ranges from 0-30 with higher scores indicating less cognitive impairment. Scores ranging from 18-25 indicate mild cognitive impairment, 10-17 indicate moderate cognitive impairment, and scores less than 10 indicate severe cognitive impairment.

3. Voice-Handicap Index [All participants completed the VHI once pre-operatively and once 1 year post-operatively (after the 6-month open unblinded phase).]

   The Voice-Handicap Index (VHI) is a questionnaire that measures the patients' perceived degree of handicap related to their voice. The VHI ranges from a scale of 0-100, with higher scores reflecting higher perceived degree of voice handicap and lower scores reflecting lower perceived degree of voice handicap.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinically diagnosed isolated laryngeal dystonia (adductor spasmodic dysphonia)

• Able to give informed consent

• Patients who fall into the age range of 18-75 years old

• Patients with inadequate medical and BTX management of spasmodic dysphonia

Exclusion Criteria:

• Dystonia present in other body parts (i.e- eyes, neck, limbs) in addition to larynx

• History of laryngeal denervation surgery for spasmodic dysphonia

• History of intracranial pathology (such as multiple sclerosis, tumors, or aneurysms) that may account for dystonia or essential tremor.

• History or evidence of ongoing psychiatric or neurodegenerative disorders (such as Parkinson's disease, Alzheimer's disease).

• Incompetent adults or those unable to communicate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 4E3

Sponsors and Collaborators

• University of British Columbia

Investigators

• Principal Investigator: Christopher R Honey, MD, DPhil, UBC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 24, 2017

More Information

Publications

• Ludlow CL, Adler CH, Berke GS, Bielamowicz SA, Blitzer A, Bressman SB, Hallett M, Jinnah HA, Juergens U, Martin SB, Perlmutter JS, Sapienza C, Singleton A, Tanner CM, Woodson GE. Research priorities in spasmodic dysphonia. Otolaryngol Head Neck Surg. 2008 Oct;139(4):495-505. doi: 10.1016/j.otohns.2008.05.624. Review.
• 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. Epub 2007 Dec 14.

• Responsible Party: Christopher Honey, Neurosurgeon, Professor of Surgery (Neurosurgery), Director of Surgical Centre for Movement Disorders, University of British Columbia
• ClinicalTrials.gov Identifier: NCT02558634
• Other Study ID Numbers: H15-02535
• First Posted: Sep 24, 2015
• Last Update Posted: Jun 14, 2022
• Last Verified: May 1, 2022

• Additional relevant MeSH terms: Dysphonia; Hoarseness; Dystonia

Study Results

Participant Flow

Arm/Group Title	DBS-on First, Then DBS-off (Sham-stimulation)	DBS-off First (Sham-stimulation), Then DBS-on
Arm/Group Description	Ventral intermediate Nucleus (VIM) Thalamic DBS on for the first 3 months, then Thalamic DBS off for the next 3 months DBS system includes: Implantable Pulse Generator (IPG) DBS Lead DBS Lead Extension Kit VIM Thalamic DBS ON for first 3 months, then Thalamic DBS OFF for following 3 months	Ventral intermediate Nucleus (VIM) Thalamic DBS off (Sham-stimulation) for the first 3 months, then Thalamic DBS on for the following 3 months DBS system includes: Implantable Pulse Generator (IPG) DBS Lead DBS Lead Extension Kit VIM Thalamic Deep Brain Stimulation OFF for first 3 months, followed by VIM Thalamic Deep Brain Stimulation ON for the following 3 months
Period Title: Blinded: First Intervention (3 Months)
STARTED	4	2
COMPLETED	4	2
NOT COMPLETED	0	0
Period Title: Blinded: First Intervention (3 Months)
STARTED	4	2
COMPLETED	3	2
NOT COMPLETED	1	0
Period Title: Blinded: First Intervention (3 Months)
STARTED	4	2
COMPLETED	4	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Patients who are currently receiving BTX injections for their voice disorder Who experience fluctuations in their symptom control as a result of their BTX therapy Patients who fall into the age range of 18-75 years old
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.17 (8.27)
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
Canada	6 100%
Patients who are currently receiving BTX injections for their voice disorder (Count of Participants)
Count of Participants [Participants]	6 100%
Patients who experience fluctuations in their symptom control as a result of their BTX therapy (Count of Participants)
Count of Participants [Participants]	6 100%

Outcome Measures

1. Primary Outcome

Title	Unified Spasmodic Dysphonia Rating Scale (USDRS)
Description	Assessments of spasmodic dysphonia using a standardized spasmodic dysphonia rating scale were done pre-operatively, blinded DBS ON, blinded DBS OFF, and open DBS ON. Voice recording taken of each patient reading standardized sentences were blinded and evaluated by two speech language pathologists. The scale ranges from 0-7, with lower scores being better and higher scores being worse.
Time Frame	After the first 6 months, the participants completed the USDRS twice (once per crossover).

Outcome Measure Data

Analysis Population Description

One patient requested to have their DBS on after 2 weeks of being in the blinded-DBS OFF after the first crossover.

Arm/Group Title	Blinded-DBS ON	Blinded-DBS OFF
Arm/Group Description	All participants who at some point in the study were in the 3-month blinded DBS ON intervention.	All participants who at some point in the study were in the 3-month blinded DBS OFF intervention.
Measure Participants	6	5
Median (Standard Deviation) [units on a scale]	2.5 (1.4)	3.75 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded-DBS ON
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	The level of significance was set at p=0.025 to allow a Bonferroni correction for these two tests (i.e. p=0.050 divided by two).
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Voice-Related Quality of Life
Description	Double-blinded assessments of voice-related quality of life with DBS ON/OFF were conducted using the V-RQoL for Spasmodic Dysphonia. The V-RQoL is a questionnaire that measures a patient's voice related quality of life. The scale ranges from 0-50, with higher scores representing a lower quality of life with respect to voice.
Time Frame	After the first 6 months, the participants completed the V-RQoL twice (once per crossover).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Blinded-DBS ON	Blinded-DBS OFF
Arm/Group Description	All participants who at some point in the study were in the 3-month blinded DBS ON intervention.	All participants who at some point in the study were in the 3-month blinded DBS OFF intervention.
Measure Participants	6	5
Median (Standard Deviation) [units on a scale]	74.7 (18.3)	19 (18.2)

3. Secondary Outcome

Title	Beck's Depression Inventory Scale
Description	Beck's Depression Inventory Scale (BDI-II) was used in this study to evaluate the mood of the patients both pre-operatively and at the end of the one-year study. All 6 patients completed the BDI-II, which is a scale that identifies symptoms and attitudes associated with depression, and evaluates the presence and severity of depression. The BDI-II ranges from 0-63. Scores ranging from 0-10 are considered to be absent or minimal depression, 10-18 indicate mild to moderate depression, 19-29 indicate moderate depression, and 30-63 indicate severe depression.
Time Frame	All participants completed the BDI-II once pre-operatively and once 1 year post-operatively (after the 6-month open unblinded phase).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open-DBS ON
Arm/Group Description	All participants in the study were assessed using the BDI-II pre-operatively and then again at the end of the 6-month open DBS ON phase (1 year post-op).
Measure Participants	6
Pre-Operative BDI-II	13.33 (7.20)
One Year Follow-Up BDI-II	6.50 (6.47)

4. Secondary Outcome

Title	Montreal Cognitive Assessment Scale (MoCA)
Description	The MoCA was used to analyze the cognitive ability of the patients. It was first evaluated pre-operatively and again evaluated at the end of the one-year study. The MoCA scale ranges from 0-30 with higher scores indicating less cognitive impairment. Scores ranging from 18-25 indicate mild cognitive impairment, 10-17 indicate moderate cognitive impairment, and scores less than 10 indicate severe cognitive impairment.
Time Frame	All participants completed the MoCA once pre-operatively and once 1 year post-operatively (after the 6-month open unblinded phase).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open-DBS ON
Arm/Group Description	All participants in the study were assessed using the MoCA pre-operatively and then again at the end of the 6-month open DBS ON phase (1 year post-op).
Measure Participants	6
Pre-Operative MoCA	24.17 (3.08)
One Year Follow-Up MoCA	26.67 (3.09)

5. Secondary Outcome

Title	Voice-Handicap Index
Description	The Voice-Handicap Index (VHI) is a questionnaire that measures the patients' perceived degree of handicap related to their voice. The VHI ranges from a scale of 0-100, with higher scores reflecting higher perceived degree of voice handicap and lower scores reflecting lower perceived degree of voice handicap.
Time Frame	All participants completed the VHI once pre-operatively and once 1 year post-operatively (after the 6-month open unblinded phase).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open-DBS ON
Arm/Group Description	All participants in the study were assessed using the VHI pre-operatively and then again at the end of the 6-month open DBS ON phase (1 year post-op).
Measure Participants	6
Pre-Operative VHI	84.83 (15.52)
1 Year Post-Operative VHI	38.17 (13.15)

Adverse Events

Time Frame	The study took place from January 1, 2017 - May 30, 2018. The study duration was approximately 1.5 years.
Adverse Event Reporting Description	This cohort continues to be followed and any future adverse events will be reported.
Arm/Group Title	Blinded DBS-ON		Blinded DBS-OFF		Open DBS-ON
Arm/Group Description	When DBS was turned on, none of the patients had any adverse clinical events during the trial. There were no asymptomatic hemorrhages detected on the post-operative CT scans. At the conclusion of the trial (1-year post-operative), there had been no infections, erosions, or technical malfunctions. The cohort continues to be followed and future adverse event will be reported.		When DBS was turned off, none of the patients had any adverse clinical events during the trial. There were no asymptomatic hemorrhages detected on the post-operative CT scans. At the conclusion of the trial (1-year post-operative), there had been no infections, erosions, or technical malfunctions. The cohort continues to be followed and future adverse event will be reported.		When DBS was turned on, none of the patients had any adverse clinical events during the trial. There were no asymptomatic hemorrhages detected on the post-operative CT scans. At the conclusion of the trial (1-year post-operative), there had been no infections, erosions, or technical malfunctions. The cohort continues to be followed and future adverse event will be reported.
All Cause Mortality
	Blinded DBS-ON		Blinded DBS-OFF		Open DBS-ON
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Blinded DBS-ON		Blinded DBS-OFF		Open DBS-ON
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Blinded DBS-ON		Blinded DBS-OFF		Open DBS-ON
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.