REducing SPEECH-related Side-effects of Deep Brain Stimulation in Parkinson's Disease Via Automated Speech Analysis (RESPEECH-PD)

The investigators' objective is to improve L-dopa sensitive PD-related dysarthria and at the same time reduce DBS-induced speech disorders with the help of automated acoustic analysis in patients with STN-DBS-induced dysarthria.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: Change of stimulation amplitudes in dopaminergic OFF drug state

Detailed Description

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment of L-dopa sensitive motor symptoms of Parkinson's disease (PD) but its effects on speech are equivocal. Although some aspects of speech might improve with STN-DBS, stimulation-induced dysarthria represents one of the most common side effects, with a prevalence of up to 90%. Worsening of speech can neutralize the motor benefits of STN-DBS in terms of overall benefit in quality of life. STN-DBS induced dysarthria is not understood in sufficient detail that would allow its prevention or sustained reduction. The human ear is too limited in quantifying subtle changes in speech and to differentiate between parkinsonian and stimulation induced dysarthria. The investigators' objective is to improve L-dopa sensitive PD-related dysarthria and at the same time reduce DBS-induced speech disorders with the help of automated acoustic analysis in patients with STN-DBS-induced dysarthria.

In Part 1, the investigators' aim is to identify the most sensitive and specific speech variables for STN-DBS-related improvement of parkinsonian dysarthria and STN-DBS-induced speech-related side-effects, by application of an automated acoustic speech analysis technique. Patients with STN-DSB induced dysarthria will be examined in their medication ON state. Where possible the study will also be performed in the medication OFF state (after an overnight withdrawal of their PD medication). In both states, speech analysis will be performed in the stimulation OFF and ON states, as well as with increasing stimulation amplitudes.

In Part 2, the investigators' aim at investigating the anatomical and pathophysiological substrates of STN-DBS induced changes in speech production, by establishing stimulation maps. Stimulation maps highlight effective regions of stimulation and can help clinicians to navigate and program DBS steering the current towards the target region that improves speech (here a priori the sensorimotor STN for improving parkinsonian speech together with other parkinsonian signs), while avoiding current diffusion to regions identified as potentially worsening speech.

Part 3 is explorative. The investigators' hypothesize, that selected speech variables in automated speech analysis (as identified in part 1+2) are more sensitive to improvement of STN-DBS induced dysarthria, than ratings of three blinded speech-therapists. Again patients with STN-DBS induced dysarthria will be recruited to this study (willing participants of part 1+2 and patients who did not participate in part 1+2 will be included). The investigators will assess dysarthria by automated speech analysis, expert ratings and subjective ratings, before (at baseline visit) and at two time points (at V1 between 0-6 weeks after baseline and at V2 between 6-12 weeks after V1) after measures are taken to reduce stimulation induced dysarthria. Measures to reduce STN-DBS induced dysarthria will include all DBS settings that are routinely applied in daily clinical practice for dysarthria reduction. DBS-settings will be performed on both DBS-leads and patients will be in the medication ON state.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paul Krack, Prof.; Phone Number: +41 31 632 21 68; Email: paul.krack@insel.ch
• Study Contact Backup: Name: Mario Sousa, MD; Phone Number: +41 31 664 23 49; Email: mario.sousa@insel.ch

Study Locations

• Czechia
  • Prague, Czechia, 166 27
    • Active, not recruiting
    • Czech Technical University Prague
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • University Hospital Inselspital, Berne
    • Contact: Paul Krack, Prof.; Phone Number: +41 31 632 21 68; Email: paul.krack@insel.ch
    • Contact: Mario Sousa, MD; Phone Number: +41 31 664 23 49; Email: mario.sousa@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Idiopathic Parkinson-Syndrome according to the Movement Disorders Society Criteria
• Treatment with bilateral deep brain stimulation in the subthalamic nucleus (for parts 1, 2 and 3)
• Time since DBS-STN operation ≥ 3 month (for parts 1, 2 and 3)
• Able to give informed consent as documented by signature
• Fluent in Swiss-German or German
• STN-DBS-induced dysarthria. In an operational definition, all PD-patients who reported -worsening of speech time-locked to STN-DBS implantation or patients with dysarthria on chronic stimulation improving with reduction of stimulation amplitudes in the context of postoperative routine follow up will be defined as having STN-DBS-induced dysarthria

Exclusion Criteria:

• Dysarthria caused in addition by a condition other than PD or DBS (e.g. stroke, myasthenia)
• Clinical diagnosis of aphasia
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders and dementia. A Montreal Cognitive Assesment (MoCa) will be performed and patients with ≤ 20 of 30 points will be excluded
• Change of parkinsonian medication in the last four weeks prior to inclusion in part 1 and 3
• Change of STN-DBS parameters in the last four weeks prior to inclusion (for parts 1 and 3)
• Depression with acute suicidal ideation
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: All participants; All participants who will participate in part 1.	Other: Change of stimulation amplitudes in dopaminergic OFF drug state; Change of stimulation amplitudes during experiment in dopaminergic OFF drug state.
No Intervention: Part 2: All participants; All participants who participated in part 1
No Intervention: Part 3: All participants; All participants who will participate in part 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Identification of the most sensitive and specific speech variables	Identification of the most sensitive and specific speech variables of an automated acoustic analysis method, for STN-DBS-related improvement as well as worsening of speech in PD patients, under the two conditions (dopaminergic ON and OFF drug state). Speech variables will be extracted from the automated acoustic analysis.	At visit 1 (baseline visit)
Part 1: Identification of the most sensitive and specific speech variables	Identification of the most sensitive and specific speech variables of an automated acoustic analysis method, for STN-DBS-related improvement as well as worsening of speech in PD patients, under the two conditions (dopaminergic ON and OFF drug state). Speech variables will be extracted from the automated acoustic analysis.	At visit 2 (≤4 weeks after visit 1)
Part 2, Speech analysis: Investigation of spatial overlap of volume of tissue activated (VTA) and the corticobulbar/corticospinal tract	Investigation of spatial overlap of tissue activated (VTA) and the corticobulbar/corticospinal tract, in relation to the dysarthria-worsening.	12 months
Part 2, Speech analysis: Investigation of spatial overlap of VTA and the dorsolateral (sensorimotor) STN	Investigation of spatial overlap of VTA and the dorsolateral (sensorimotor) STN in relation to improvement of PD-related dysarthria.	12 months
Part 3: Perceptual speech ratings	To test if the model 'perceptual speech ratings' explains subjective improvement of STN-DBS induced dysarthria. Perceptive rating will be performed by three experienced speech therapists, who will rate speech on a visual analogue scale (VAS).	At baseline visit
Part 3: Perceptual speech ratings	To test if the model 'perceptual speech ratings' explains subjective improvement of STN-DBS induced dysarthria. Perceptive rating will be performed by three experienced speech therapists, who will rate speech on a visual analogue scale (VAS).	At visit 1 (0-6 weeks after baseline)
Part 3: Perceptual speech ratings	To test if the model 'perceptual speech ratings' explains subjective improvement of STN-DBS induced dysarthria. Perceptive rating will be performed by three experienced speech therapists, who will rate speech on a visual analogue scale (VAS).	At visit 2 (6-12 weeks after visit 1)
Part 3: Automated speech analysis	To test if the model 'automated speech analysis' explains subjective improvement of STN-DBS induced dysarthria. From the automated speech analysis, only the speech parameters explaining most of the variance in the model from part 2 will be included in the analysis.	At baseline visit
Part 3: Automated speech analysis	To test if the model 'automated speech analysis' explains subjective improvement of STN-DBS induced dysarthria. From the automated speech analysis, only the speech parameters explaining most of the variance in the model from part 2 will be included in the analysis.	At visit 1 (0-6 weeks after baseline)
Part 3: Automated speech analysis	To test if the model 'automated speech analysis' explains subjective improvement of STN-DBS induced dysarthria. From the automated speech analysis, only the speech parameters explaining most of the variance in the model from part 2 will be included in the analysis.	At visit 2 (6-12 weeks after visit 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Subjective rating of the quality of speech	Subjective rating of the quality of speech on a numeric rating scale by the patient, ranging from 0 = no impairment to 10 = maximum conceivable impairment of speech. Assessment will be performed under the two conditions (dopaminergic ON and OFF drug state).	At visit 1 (baseline visit) and visit 2 (≤4 weeks)
Part 1: Assessment parkinsonism contralateral to the tested DBS lead	Assessment parkinsonism contralateral to the tested DBS lead using items 3.4 (finger tapping), 3.5 (hand movements), 3.7 (toe tapping) and 3.8 (leg agility) of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS part III) for the limbs contralateral to the tested DBS electrode. Assessment will be performed under the two conditions (dopaminergic ON and OFF drug state).	At visit 1 (baseline visit) and visit 2 (≤4 weeks)
Part 1: Clinical assessment of possible side effects	Noting possible side effects that may occur during the experiment, such as fascial spasm or contraction of the hand muscles. Assessment will be performed under the two conditions (dopaminergic ON and OFF drug state).	At visit 1 (baseline visit) and visit 2 (≤4 weeks)
Part 3: Subjective rating of the quality of speech	Subjective rating of the quality of speech on a numeric rating scale by the patient, ranging from 0 = no impairment to 10 = maximum conceivable impairment of speech.	At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)
Part 3: Assessment of motoric symptoms	Assessment of Parkinsonism using the full Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS part III).	At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)
Part 3: Clinical assessment of possible side effects	Noting possible side effects that may occur during the experiment, such as fascial spasm or contraction of the hand muscles.	At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Czech Technical University in Prague
• Investigators: Principal Investigator: Paul Krack, Prof., University Hospital Inselspital, Berne

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Anticipated): November 30, 2023
• Study Completion (Anticipated): February 29, 2024

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): January 10, 2022

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Speech; Deep brain stimulation; Dysarthria; Automated speech analysis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Dopamine; Dopamine Agonists
• Other Study ID Numbers: 2021-01787

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No