Clinical trial NCT05182892: REducing SPEECH-related Side-effects of Deep Brain Stimulation in Parkinson's Disease Via Automated Speech Analysis
Official title: REducing SPEECH-related Side-effects of Deep Brain Stimulation in Parkinson's Disease Via Automated Speech Analysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: Deep brain stimulation
Speech
Dysarthria
Automated speech analysis
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Czech Technical University in Prague
First posted: 2022-01-10
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Identification of the most sensitive and specific speech variables
timeFrame: At visit 1 (baseline visit)
measure: Part 1: Identification of the most sensitive and specific speech variables
timeFrame: At visit 2 (≤4 weeks after visit 1)
measure: Part 2, Speech analysis: Investigation of spatial overlap of volume of tissue activated (VTA) and the corticobulbar/corticospinal tract
timeFrame: 12 months
measure: Part 2, Speech analysis: Investigation of spatial overlap of VTA and the dorsolateral (sensorimotor) STN
timeFrame: 12 months
measure: Part 3: Perceptual speech ratings
timeFrame: At baseline visit
measure: Part 3: Perceptual speech ratings
timeFrame: At visit 1 (0-6 weeks after baseline)
measure: Part 3: Perceptual speech ratings
timeFrame: At visit 2 (6-12 weeks after visit 1)
measure: Part 3: Automated speech analysis
timeFrame: At baseline visit
measure: Part 3: Automated speech analysis
timeFrame: At visit 1 (0-6 weeks after baseline)
measure: Part 3: Automated speech analysis
timeFrame: At visit 2 (6-12 weeks after visit 1)
Secondary outcomes:
measure: Part 1: Subjective rating of the quality of speech
timeFrame: At visit 1 (baseline visit) and visit 2 (≤4 weeks)
measure: Part 1: Assessment parkinsonism contralateral to the tested DBS lead
timeFrame: At visit 1 (baseline visit) and visit 2 (≤4 weeks)
measure: Part 1: Clinical assessment of possible side effects
timeFrame: At visit 1 (baseline visit) and visit 2 (≤4 weeks)
measure: Part 3: Subjective rating of the quality of speech
timeFrame: At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)
measure: Part 3: Assessment of motoric symptoms
timeFrame: At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)
measure: Part 3: Clinical assessment of possible side effects
timeFrame: At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Czech Technical University Prague
city: Bern
country: Switzerland
facility: University Hospital Inselspital, Berne
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Paul Krack, Prof.
role: PRINCIPAL_INVESTIGATOR
References: