Non-invasive Brain Stimulation for the Treatment of Mild Cognitive Impairment in Parkinson's Disease

NCT06399731 | Recruiting DMC

• 3 other identifiers: 2023.080410390052210003NL84843.018.23
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This cross-over pilot study aims to study the acceptability of two methods of non-invasive brain stimulation for the treatment of Parkinson's disease mild cognitive impairment (PD-MCI) - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) targeted at the left dorsolateral prefrontal cortex (DLPFC). Twenty participants will undergo both interventions in a cross-over design. They sequentially undergo four consecutive phases (4 weeks each), 1) no-intervention baseline, 2) rTMS ór tDCS, 3) no-intervention, 4) second intervention. The primary outcome measure will be acceptability of the interventions, and secondary outcomes include feasibility, cognitive function, neuropsychiatric symptoms, motor function. We will use MRI to explore personalized targeting.

Conditions

Parkinson Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Quantative acceptability of the interventions (measured seperately)

  Measured with Theoretical Framework of Acceptability questionnaire ("TFA-PD questionnaire") score, measuring seven domains of acceptability

  Eight weeks and sixteen weeks (after first and second intervention)

Secondary Outcomes (21)

• Qualitative acceptability assessment of both interventions

  After study termination (i.e., all participants finished)

• Intervention compliance (feasibility)

  Eight weeks and sixteen weeks (during first and second intervention)

• Intervention attrition (feasibility)

  After study termination (i.e., all participants finished)

• Usability of the tDCS device (feasibility)

  Eight weeks or sixteen weeks (after tDCS intervention)

• Subjective cognitive function

  Four, eight, twelve and sixteen weeks

Other Outcomes (17)

• Structural and functional connectivity

  Baseline

• Distance to optimal DLPFC stimulation target

  Baseline

• Age

  Baseline

Study Arms (2)

Intervention arm 1: rTMS followed by tDCS

EXPERIMENTAL

Participants in intervention arm 1 will undergo four phases in the following order: 1) a no-intervention baseline phase, 2) 12 sessions of 20-minute institute-based repetitive transcranial magnetic stimulation (rTMS) (10 Hz) targeting the left DLPFC, 3) a second no-intervention baseline phase, 4) 20 sessions of 20-minute at-home anodal high-definition transcranial direct current stimulation (tDCS) targeting the left DLPFC. All phases have a duration of 4 weeks.

Device: High-frequency (10Hz) rTMS; Device: Anodal tDCS

Intervention arm 2: tDCS followed by rTMS

EXPERIMENTAL

Participants in intervention arm 2 will undergo four phases in the following order: 1) a no-intervention baseline phase, 2) 20 sessions of 20-minute at-home anodal high-definition transcranial direct current stimulation (tDCS) targeting the left DLPFC, 3) a second no-intervention baseline phase, 4) 12 sessions of 20-minute institute-based repetitive transcranial magnetic stimulation (rTMS) (10 Hz) targeting the left DLPFC. All phases have a duration of 4 weeks.

Device: High-frequency (10Hz) rTMS; Device: Anodal tDCS

Interventions

High-frequency (10Hz) rTMS DEVICE

High-frequency (10 Hz) rTMS targeting the left DLPFC, based on fMRI-peak activation during performance of the Tower of London task, at 110% resting motor threshold intensity, corrected for scalp-cortex distance at the target location, for a total of 3000 pulses per session, using 30 trains of 10 seconds with 30-second inter-train intervals (total duration: 20 minutes), using neuronavigation to record the pulse location.

Intervention arm 1: rTMS followed by tDCS; Intervention arm 2: tDCS followed by rTMS

Anodal tDCS DEVICE

Anodal high-definition tDCS. The anode will be placed at the F3 EEG location, coordinates registered using neuronavigation on the first intervention session on-site, and cathodes at Fp1, Fz, C3 and F7, in a ring surrounding the anode, using π cm2 circular stimulation electrodes, stimulating the left DLPFC at 2 mA intensity for a duration of 20 minutes, 15 s ramp up and 15 s ramp down. After an initial on-site instructional tDCS session, the tDCS intervention will be delivered at home, in part remotely-supervised via MS Teams.

Intervention arm 1: rTMS followed by tDCS; Intervention arm 2: tDCS followed by rTMS

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of Parkinson's disease, diagnosed by a neurologist;
• Mild to moderate disease stage (Hoehn \& Yahr disease stage \< 4);
• Movement Disorders Society level I criteria for PD-MCI (Litvan et al., 2012):
• Montreal Cognitive Assessment score range \[21-25\] (Dalrymple-Alford et al., 2010), or
• performance 1-2 SD below appropriate norms on at least 2 neuropsychological tests, or
• classification of PD-MCI based on recent (\< 6 months previous to participation) neuropsychological assessment taken elsewhere (report will be requested);- In case of (dopaminergic) medication use, participants are on stable medication for at least one month before participation and expect to remain on stable medication during the study

You may not qualify if:

• Indication for dementia based on the SAGE (cut-off ≤ 14; Scharre et al., 2010);
• Severe depressive disorder (Beck Depression Inventory - Ib score \> 18);
• Psychotic disorder (except for benign hallucinations with insight), screened with the Scale for Assessment of Positive Symptoms for Parkinson's disease;
• Indication of alcohol or drug abuse;
• Contra-indication for rTMS according to Magstim Rapid2 Manual; rTMS should not be:
• used on or in the vicinity of patients or users with cardiac demand pacemakers, implanted medication pumps, cochlear devices, implanted defibrillators and/or implanted neurostimulators
• used on or in the vicinity of patients with implanted metal objects• used on patients where the skin in the area to be contacted is broken
• used on those with large ischaemic scars
• used on pregnant women
• used on infants under the age of 2 years
• used on epileptic individuals
• used on those with a family history of convulsions
• used on individuals with brain lesions that could affect seizure threshold
• used on individuals suffering from multiple sclerosis
• used on individuals taking tricyclic antidepressants, neuroleptic agents or any other drug that could lower seizure threshold,

Sponsors & Collaborators

• Amsterdam UMC: lead

Study Sites (1)

Amsterdam UMC

Amsterdam, North Holland, Netherlands

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Tim D van Balkom, PhD

CONTACT

+31204441162; t.vanbalkom@amsterdamumc.nl

Chris Vriend, PhD

CONTACT

+31204441162; c.vriend@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Post-doctoral researcher

Model Details: Four consecutive phases: 1) a no-intervention baseline phase, 2) rTMS or tDCS, 3) a second no-intervention baseline phase, 4) the second NIBS intervention. All phases have a duration of 4 weeks and the order of the NIBS interventions is counterbalanced.

Study Record Dates

• First Submitted: May 1, 2024
• First Posted: May 6, 2024
• Study Start: May 31, 2024
• Primary Completion: December 1, 2025
• Study Completion: May 1, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Anonymized data will be made available after full data collection has finished, when first data cleaning has been performed and the primary endpoint analyses have been performed.
• Access Criteria: A data sharing agreement or equivalent will be set up.

Locations

NL (1)