Parkinson DiseaseSAI-PD22NCT06835595
TMS-related Measures as Biomarker of Cognitive Impairment in PD
A study testing Transcranial Magnetic Stimulation in people with Parkinson Disease, run by Azienda Sanitaria Universitaria Integrata del Trentino at 3 sites in Italy.
Trial summary
The goal of the present study is to explore the diagnostic and prognostic value of neurophysiological biomarkers obtained through paired-pulse Transcranial Magnetic Stimulation (TMS) techniques in individuals affected by Parkinson's disease (PD) with and without cognitive decline. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Transcranial Magnetic Stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 3 sitesItaly
- Study dates
- 10 Sep 2025to 1 Jan 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Ability to undergo an extensive neuropsychological evaluation
- Ability to sign informed consent for the study
- Diagnosed with idiopathic PD according to the latest revision of the MDS criteria
- On stable and optimal antiparkinsonian therapy for at least four weeks
Who cannot join
- Systemic diseases of significant severity, including cardiovascular and cerebrovascular conditions (e.g., active neoplasms requiring chemotherapy, or end-stage heart failure)
- Presence of any active neurological disease, in addition to PD
- Presence of a cochlear implant, ferromagnetic brain device or near the site of brain stimulation, pacemaker, brain electrodes for DBS, electromechanical devices with IPG, or any other implantable stimulator, including peripheral ones
- History of epilepsy
- History of cerebrovascular, tumor-related, infectious, or metabolic brain conditions predisposing to seizures or causing symptomatic epilepsy
- Pregnancy or breastfeeding
Show all 11Show fewer
- Alcoholism
- Treatment with anticholinesterase drugs, benzodiazepines, neuroleptics, anticholinergics, or antidepressants in the last month
- Treatment with drugs that lower the seizure threshold (e.g., imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, MDMA, ecstasy, phencyclidine, ketamine, gamma-hydroxybutyrate, alcohol, theophylline)
- Active cochlear pathology (especially if currently receiving ototoxic drugs, such as aminoglycoside antibiotics)
- Dementia according to the latest revision of the MDS criteria for PDD
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy3 sites, 3 recruiting
- Not yet recruiting
UOC Neuroriabilitazione - Azienda Sanitaria dell'Alto Adige
Sterzing, Trentino-Alto Adige, 39049
Viviana Versace, MD, +39 0472 774 100, viviana.versace@sabes.it
Davide Ferrazzoli, MD, +39 0472 774 100, davide.ferrazzoli@sabes.it
- Recruiting
UOC Neurologia - Azienda Provinciale per i Servizi Sanitari (APSS)
Trento, Trentino-Alto Adige, 38122
Ruggero Bacchin, MD, +39-0461903281, ruggero.bacchin@apss.tn.it
Stefania Campostrini, Mac, +39-0461903281, stefania.campostrini@apss.tn.it
- Not yet recruiting
SC Clinica Neurologica - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI)
Trieste, Friuli Venezia Giulia
Paolo Manganotti, MD, +39-0403994282, paolo.manganotti@asugi.sanita.fvg.it
Alberto Benussi, MD, +39-0403994282, alberto.benussi@asugi.sanita.fvg.it
About this study
Official title: Transcranial Magnetic Stimulation (TMS) Related Measures as Biomarker of Cognitive Impairment in Parkinson's Disease (PD)
The goal of the present study is to explore the diagnostic and prognostic value of neurophysiological biomarkers obtained through paired-pulse Transcranial Magnetic Stimulation (TMS) techniques in individuals affected by Parkinson's disease (PD) with and without cognitive decline.
The main questions it aims to answer are:
- TMS measures of cortical excitability are able to distinguish between PD patients cognitively normal, PD-Mild Cognitive Impairment (PD-MCI) and PD-Dementia (PD-D)?
- TMS measures of cortical excitability are able to predict progression of PD patient cognitive status from cognitively normal to PD-MCI and PD-D?
Read the detailed description
Parkinson's disease (PD) is the second most common degenerative disease in the world, affecting approximately 10 million people globally. Cognitive decline is considered one of the most frequent non-motor symptoms, reaching a prevalence of 80% in patients with advanced stages of the disease. Cognitive impairment represents one of the most challenging symptoms for patients, caregivers, and society. The pathophysiology underlying cognitive impairment in PD is still not fully understood.
From a neuro-transmission system perspective, cognitive decline appears to be caused predominantly by dysfunction of three systems: dopaminergic, noradrenergic, and cholinergic. Transcranial Magnetic Stimulation (TMS) is able to explore cortico-spinal pathway functionality, cortical excitability, as well as the integrity of different intra-cortical, transcortical, and cortico-subcortical neuro-transmission circuits. Paired-pulse techniques such as Short Interval Cortical Inhibition (SICI), Short Latency Afferent Inhibition (SAI), and Intracortical Facilitation (ICF) pair a conditioning and a test stimulus with different inter-stimulus intervals (ISI), permitting the exploration of transmission in neural circuits dependent on different neurotransmitters.
In the last 20 years, TMS has been applied to the study of patients with Alzheimer's dementia (AD), Fronto-temporal dementia (FTD), and Lewy Body dementias (LBD), in order to better understand their pathophysiological mechanisms and identify potential biomarkers to be used as surrogate endpoints in clinical trials for disease-modifying therapies. Conversely, dementia related to PD has been much less studied compared to AD, FTD, and LBD (7 studies in total and 176 patients with PD-related cognitive decline enrolled vs >40 studies in total and >1000 patients with AD, FTD, and LBD enrolled).
In PD patients with PD-related cognitive decline, cortical measures of excitability evaluated through TMS protocols included Resting Motor Threshold (RMT), Activated Motor Threshold (AMT), Silent Period (SP) from contralateral (CSP) and ipsilateral (ISP) activation, SAI, SICI, and ICF. A preliminary review of these studies revealed that the most commonly evaluated TMS measures were RMT and SAI (6 studies out of 8), and the measures that were significantly different, with a large effect size (expressed as Cohen's d > 0.7), comparing PD patients with and without cognitive decline (defined as MCI or dementia), were SAI and ICF (both reduced in patients with cognitive decline), while SICI was significantly increased only in PD patients with dementia compared to cognitively intact PD patients. No study has explored the value of these measures in predicting the evolution of cognitive decline to MCI or dementia.
The aim of the present study is to explore the diagnostic and prognostic value of neurophysiological biomarkers obtained through paired-pulse TMS techniques in individuals affected by PD. Comprehensive neurological and neuro-psychological evaluations will be performed after enrollment, in addition to a set of paired-pulse TMS tests including SAI, SICI, and ICF. Patients will be categorized according to cognitive status (cognitively normal - CN, MCI, dementia) and assessed at T0, after T1 (one year), T2 (two years), and T3 (three years). SAI, SICI, and ICF measures will be compared cross-sectionally among PD patients cognitively normal, with MCI, and dementia to assess their diagnostic value in differential diagnosis of cognitive status. Moreover, SAI, SICI, and ICF measures of patients manifesting a progression of cognitive status from cognitively normal to MCI, and from MCI to dementia at follow-ups, will be compared with those of patients not manifesting a progression of cognitive status, to assess their value in predicting the evolution of cognitive status.
- Conditions
- Parkinson Disease
- Being tested
- Transcranial Magnetic Stimulation
- Keywords
- Parkinson's, Neurologic Manifestations, Parkinson Disease, Neurodegenerative Diseases, Movement Disorders, Basal Ganglia Diseases, Brain Diseases, Neurotransmitter Agents, Transcranial Magnetic Stimulation, Sensory Motor Integration, Cortical Excitability
- Medical subject headings
- Parkinson Disease, Neurologic Manifestations, Neurodegenerative Diseases, Movement Disorders, Basal Ganglia Diseases, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDiagnostic test
Paired stimulation protocols of TMS to collect SAI, SICI, ICF measures
| Study group | Role | What they receive |
|---|---|---|
| PD patients cognitively normal (PD-CN) | Experimental | PD patients with a normal cognitive functioning and with preserved autonomy in activity of daily living will be subjected to paired-pulse protocols of TMS for the assessment of SAI, SICI and ICF
PD patients with a mild cognitive functioning but with a preserved autonomy in activity of daily living will be subjected to paired-pulse protocols of TMS for the assessment of SAI, SICI and ICF Receives: Diagnostic Test: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare SAI, SICI and ICF among PD patients who cognitively progressed from normal cognitive status to MCI or dementia, and from MCI to dementia.
Paired-pulse Trans-cranial magnetic stimulation techniques (Short-Latency Afferent Inhibition - SAI), Short-Interval Intracortical Inhibition - SICI, and Intra-Cortical Facilitation - ICF.
Measured: Three timepoints: one, two or three-year follow-up (respectively T1, T2, T3)
To compare SAI, SICI and ICF among PD patients with different cognitive condition (normal, MCI and dementia).
Paired-pulse Trans-cranial magnetic stimulation techniques (Short-Latency Afferent Inhibition - SAI), Short-Interval Intracortical Inhibition - SICI, and Intra-Cortical Facilitation - ICF.
Measured: Four timepoints: at baseline (T0), and at one, two or three-year follow-up (respectively T1, T2, T3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2025
- Study start10 Sep 2025
- Primary completion1 Jan 2029 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Sanitaria Universitaria Integrata del Trentino
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luigi Cattaneo, MD, PhD, Study director, CIMEC - Centro Interdipartimentale Mente Cervello - Università degli studi di TrentoRuggero Bacchin, MD, Principal investigator, UOC Neurologia - Azienda Sanitaria per i Servizi Sanitari (APSS)Bruno Giometto, MD, Study chair, CISMED - Centro Interdipartimentale di Scienze Mediche - Università degli studi di Trento
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06835595
- Sponsor's protocol ID
- A969
- Other IDs
- SAIPD22
- Acronym
- SAI-PD22
- Status last verified
- Dec 2025
- First submitted
- 14 Feb 2025
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation (TMS) Related Measures as Biomarker of Cognitive Impairment in Parkinson's Disease (PD)
- ClinicalTrials.gov ID
- NCT06835595
- Acronym / sponsor ID
- SAI-PD22 / A969
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's, Neurologic Manifestations, Parkinson Disease, Neurodegenerative Diseases, Movement Disorders, Basal Ganglia Diseases, Brain Diseases, Neurotransmitter Agents
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Azienda Sanitaria Universitaria Integrata del TrentinoUniversity, hospital or other
- Study start
- 10 Sep 2025 (actual)
- Primary completion
- 1 Jan 2029 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 19 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the present study is to explore the diagnostic and prognostic value of neurophysiological biomarkers obtained through paired-pulse Transcranial Magnetic Stimulation (TMS) techniques in individuals affected by Parkinson's disease (PD) with and without cognitive decline.
The main questions it aims to answer are:
- TMS measures of cortical excitability are able to distinguish between PD patients cognitively normal, PD-Mild Cognitive Impairment (PD-MCI) and PD-Dementia (PD-D)?
- TMS measures of cortical excitability are able to predict progression of PD patient cognitive status from cognitively normal to PD-MCI and PD-D?
Detailed description
Parkinson's disease (PD) is the second most common degenerative disease in the world, affecting approximately 10 million people globally. Cognitive decline is considered one of the most frequent non-motor symptoms, reaching a prevalence of 80% in patients with advanced stages of the disease. Cognitive impairment represents one of the most challenging symptoms for patients, caregivers, and society. The pathophysiology underlying cognitive impairment in PD is still not fully understood.
From a neuro-transmission system perspective, cognitive decline appears to be caused predominantly by dysfunction of three systems: dopaminergic, noradrenergic, and cholinergic. Transcranial Magnetic Stimulation (TMS) is able to explore cortico-spinal pathway functionality, cortical excitability, as well as the integrity of different intra-cortical, transcortical, and cortico-subcortical neuro-transmission circuits. Paired-pulse techniques such as Short Interval Cortical Inhibition (SICI), Short Latency Afferent Inhibition (SAI), and Intracortical Facilitation (ICF) pair a conditioning and a test stimulus with different inter-stimulus intervals (ISI), permitting the exploration of transmission in neural circuits dependent on different neurotransmitters.
In the last 20 years, TMS has been applied to the study of patients with Alzheimer's dementia (AD), Fronto-temporal dementia (FTD), and Lewy Body dementias (LBD), in order to better understand their pathophysiological mechanisms and identify potential biomarkers to be used as surrogate endpoints in clinical trials for disease-modifying therapies. Conversely, dementia related to PD has been much less studied compared to AD, FTD, and LBD (7 studies in total and 176 patients with PD-related cognitive decline enrolled vs >40 studies in total and >1000 patients with AD, FTD, and LBD enrolled).
In PD patients with PD-related cognitive decline, cortical measures of excitability evaluated through TMS protocols included Resting Motor Threshold (RMT), Activated Motor Threshold (AMT), Silent Period (SP) from contralateral (CSP) and ipsilateral (ISP) activation, SAI, SICI, and ICF. A preliminary review of these studies revealed that the most commonly evaluated TMS measures were RMT and SAI (6 studies out of 8), and the measures that were significantly different, with a large effect size (expressed as Cohen's d > 0.7), comparing PD patients with and without cognitive decline (defined as MCI or dementia), were SAI and ICF (both reduced in patients with cognitive decline), while SICI was significantly increased only in PD patients with dementia compared to cognitively intact PD patients. No study has explored the value of these measures in predicting the evolution of cognitive decline to MCI or dementia.
The aim of the present study is to explore the diagnostic and prognostic value of neurophysiological biomarkers obtained through paired-pulse TMS techniques in individuals affected by PD. Comprehensive neurological and neuro-psychological evaluations will be performed after enrollment, in addition to a set of paired-pulse TMS tests including SAI, SICI, and ICF. Patients will be categorized according to cognitive status (cognitively normal - CN, MCI, dementia) and assessed at T0, after T1 (one year), T2 (two years), and T3 (three years). SAI, SICI, and ICF measures will be compared cross-sectionally among PD patients cognitively normal, with MCI, and dementia to assess their diagnostic value in differential diagnosis of cognitive status. Moreover, SAI, SICI, and ICF measures of patients manifesting a progression of cognitive status from cognitively normal to MCI, and from MCI to dementia at follow-ups, will be compared with those of patients not manifesting a progression of cognitive status, to assess their value in predicting the evolution of cognitive status.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD patients cognitively normal (PD-CN) | Experimental | Diagnostic Test: Transcranial Magnetic StimulationPD patients with a normal cognitive functioning and with preserved autonomy in activity of daily living will be subjected to paired-pulse protocols of TMS for the assessment of SAI, SICI and ICF PD patients with a mild cognitive functioning but with a preserved autonomy in activity of daily living will be subjected to paired-pulse protocols of TMS for the assessment of SAI, SICI and ICF |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Ability to undergo an extensive neuropsychological evaluation
- Ability to sign informed consent for the study
- Diagnosed with idiopathic PD according to the latest revision of the MDS criteria
- On stable and optimal antiparkinsonian therapy for at least four weeks
Key exclusion criteria (11 listed)
- Systemic diseases of significant severity, including cardiovascular and cerebrovascular conditions (e.g., active neoplasms requiring chemotherapy, or end-stage heart failure)
- Presence of any active neurological disease, in addition to PD
- Presence of a cochlear implant, ferromagnetic brain device or near the site of brain stimulation, pacemaker, brain electrodes for DBS, electromechanical devices with IPG, or any other implantable stimulator, including peripheral ones
- History of epilepsy
- History of cerebrovascular, tumor-related, infectious, or metabolic brain conditions predisposing to seizures or causing symptomatic epilepsy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic StimulationPaired stimulation protocols of TMS to collect SAI, SICI, ICF measures | Diagnostic test | PD patients cognitively normal (PD-CN) |
Primary outcome
To compare SAI, SICI and ICF among PD patients who cognitively progressed from normal cognitive status to MCI or dementia, and from MCI to dementia.
Time frame: Three timepoints: one, two or three-year follow-up (respectively T1, T2, T3)
Paired-pulse Trans-cranial magnetic stimulation techniques (Short-Latency Afferent Inhibition - SAI), Short-Interval Intracortical Inhibition - SICI, and Intra-Cortical Facilitation - ICF.
To compare SAI, SICI and ICF among PD patients with different cognitive condition (normal, MCI and dementia).
Time frame: Four timepoints: at baseline (T0), and at one, two or three-year follow-up (respectively T1, T2, T3)
Paired-pulse Trans-cranial magnetic stimulation techniques (Short-Latency Afferent Inhibition - SAI), Short-Interval Intracortical Inhibition - SICI, and Intra-Cortical Facilitation - ICF.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Luigi Cattaneo, MD, PhD study director
CIMEC - Centro Interdipartimentale Mente Cervello - Università degli studi di Trento
Ruggero Bacchin, MD principal investigator
UOC Neurologia - Azienda Sanitaria per i Servizi Sanitari (APSS)
Bruno Giometto, MD study chair
CISMED - Centro Interdipartimentale di Scienze Mediche - Università degli studi di Trento
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Parkinson Disease, run by Azienda Sanitaria Universitaria Integrata del Trentino at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruggero Bacchin, MD (+39-0461903281, ruggero.bacchin@apss.tn.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare SAI, SICI and ICF among PD patients who cognitively progressed from normal cognitive status to MCI or dementia, and from MCI to dementia. (time frame: Three timepoints: one, two or three-year follow-up (respectively T1, T2, T3)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.