Supplementary Motor Area is a Potential Target for Speech Disturbance in Parkinson Disease

Speech disturbance is common in patients with Parkinson disease. Pharmacotherapy improves motor symptoms but has inconsistent effects on speech disturbance in PD patients. Transcranial magnetic stimulation (TMS) is a safe and non-invasive tool used for brain stimulation. Repetitive transcranial magnetic stimulation (rTMS) has positive effects on motor function of PD. Yet, its effect on speech disturbance seems to be inconclusive. Previous rTMS studies mainly focused on the primary motor cortex for PD speech disturbance. Nevertheless, we think supplementary motor area (SMA) may be a better target. Speech disturbance in PD may be associated with basal ganglia-thalamocortical motor circuits and SMA involves in the cortex part. In addition, neuroimaging studies showed that SMA were under-activation in PD patients. Therefore, we conduct this 3-year study including two experiments. The aim of the study is to determine if rTMS over SMA can improve the speech function of PD patients and change the functional connectivity of speech pathway in the brain. This will be the first study to investigate the effect of rTMS over SMA on speech.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: "MAGSTIM" Repetitive transcranial magnetic stimulator (rTMS) system

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Experiment 1

Inclusion Criteria:

• right-handed healthy adult volunteers who understand and agree on the informed consent of the study

Exclusion Criteria:

• pregnancy or possibility of pregnancy
• history of seizure
• family history of epilepsy
• metals in any part of the body.

Experiment 2

Inclusion Criteria:

• PD patients with speech disturbance who understand and agree on the informed consent of the study. The speech item scored 2 or 3 in the unified Parkinson's disease rating scale (UPDRS) part III.

Exclusion Criteria:

• dementia
• the history of stroke, brain lesion, other central nervous system diseases
• the contraindication of TMS which described above
• any contraindication of MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD patients with speech disturbance treated with 10 Hz rTMS	Device: "MAGSTIM" Repetitive transcranial magnetic stimulator (rTMS) system; we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.
Sham Comparator: PD patients with speech disturbance treated with sham rTMS	Device: "MAGSTIM" Repetitive transcranial magnetic stimulator (rTMS) system; we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.
Experimental: PD patients without speech disturbance treated with 10 Hz rTMS	Device: "MAGSTIM" Repetitive transcranial magnetic stimulator (rTMS) system; we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.
Sham Comparator: PD patients without speech disturbance with sham rTMS	Device: "MAGSTIM" Repetitive transcranial magnetic stimulator (rTMS) system; we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of speech performance from baseline in experiment 1	sustained phonation of /a/ for as long and steady as possible in one breath; fast pa-/ta-/ka- repetition at least nine times in one breath; reading a standardized paragraph composed of 80 words as clear and fast as possible	Baseline ((1) before rTMS), (2) immediately after rTMS
Change of speech performance from baseline in experiment 2	sustained phonation of /a/ for as long and steady as possible in one breath; fast pa-/ta-/ka- repetition at least nine times in one breath; reading a standardized paragraph composed of 80 words as clear and fast as possible	Baseline ((1) before rTMS), (2) within 24 hours after 10 times of rTMS (3) 8 weeks later after 10 times of rTMS
Change of functional connectivity from baseline in experiment 2	use rs-fMRI to compare the functional connectivity between PD patients with and without speech disturbance and the changes of connectivity after rTMS over SMA	Baseline ((1) before rTMS), (2) within 24 hours after 10 times of rTMS

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: transcranial magnetic stimulation; speech disturbance
• 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
• Other Study ID Numbers: 202102465A3A0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No