Biomarkers of Neurodegeneration and Neuroplasticity in Parkinson's Disease Patients Treated by Bilateral M1-iTBS

NCT06840145 | Completed

• 1 other identifier: PD-iTBS-2169-N-19
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Intermittent theta-burst stimulation (iTBS) is a promising therapeutic option for Parkinson's disease patients. A study involving 24 patients will assess its effectiveness in alleviating clinical deficits. Patients will undergo 5 sessions of iTBS over the bilateral M1 and a 3-month washout period. Motor evaluation, neurocognitive assessment, serum biomarkers of neurodegeneration and neuroplasticity, and structural and functional MRI evaluations will be conducted at follow-up visits.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Clinical motor improvement

  Movement Disorders Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) Part III (MDS-UPDRS III). Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe.

  Changes from baseline to immediately after stimulation, after 1 week, after 2 weeks, and after 4 weeks.

• Changes on quality of life and motor complications

  MDS-UPDRS (parts II - IV). Part II assessed motor experiences of daily living (Range 0-52). Part IV assessed motor complications and contained 6 items. Score range: 0-24, 4 and below is mild, 13 and above is severe

  Changes from baseline to after stimulation.

Secondary Outcomes (15)

• Change in levodopa equivalent daily dose (LEDD)

  Changes from baseline to after stimulation

• Change in the Parkinson's Fatigue Scale (PFS-16)

  Changes from baseline to after stimulation

• Change in quality of life measured with the Parkinson Disease Questionnaire-39 (PDQ-39)

  Changes from baseline to after stimulation

• Screening of cognitive function by MMP

  Changes from baseline to 2 weeks after stimulation

• Screening of frontal lobe function related activities by Frontal Assessment Battery (FAB)

  Changes from baseline to after stimulation

Other Outcomes (6)

• Resting-state EEG activity

  Changes from baseline to 3 days after stimulation

• Structural MRI - T1-weighted (T13D)

  Changes from baseline to 1 week after stimulation

• Resting-state functional fMRI

  Changes from baseline to 1 week after stimulation

Study Arms (2)

real iTBS

ACTIVE COMPARATOR

Intermittent theta burst stimulation (iTBS) will be performed using a 3 pulse bursts at 50 Hz repeated every 200 ms and delivered as short trains of 10 bursts lasting 2 s and an intertrain silence period of 8 s, for a total of 600 pulses (20 cycles of trains) and a total duration of 190 s. Intensity of iTBS will be administered to the bilateral M1 at 80% of the active motor threshold (aMT) of each patient.

Device: repetitive transcranial magnetic stimulation

sham iTBS

SHAM COMPARATOR

The repetitive transcranial magnetic stimulation (rTMS) coil stimulation will be applied in the same position of the real stimulation. Sham stimulation during treatment will follow the same procedure and both coils are identical in appearance and produce a similar sound and sensation, although the sham coil delivers no stimulation. The patient will hear the same sound of real stimulation, which will be only functionally inactive but will be completely performed (for the whole time of duration of stimulation)

Device: repetitive transcranial magnetic stimulation

Interventions

repetitive transcranial magnetic stimulation DEVICE

Intermittent theta Burst stimulation will be performed as detailed in the Real arm description

Also known as: rTMS, intermittent theta-burst stimulation, iTBS

real iTBS; sham iTBS

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with PD according to the UK Parkinson's Disease Society Brain Bank diagnostic criteria (UK PDSBB) diagnostic criteria
• Disease duration of at least 5 years to reduce the risk of including levodopa-responsive atypical Parkinsonism patients;
• Disease symptomatology in the ON medication state at a H\&Y scale of II-III;
• Clinical and therapeutic stability in the last 2 months previous to the recruitment period; and
• Aged 45-75 years.

You may not qualify if:

• Lack of a PD diagnosis that meets the UK PDSBB diagnostic criteria
• Presence of a serious systemic disease
• Presence of severe or moderate cognitive impairment comparable to dementia, as revealed by an MMP score of ≤ 24
• Any incapacitating psychiatric or other clinical condition that might affect the correct performance of this protocol, such as any dystonia and/or dyskinesia
• Patients who received amantadine within the previous 60 days
• Any sign of atypical parkinsonism, neurological comorbidities, or history of cranioencephalic traumatism or epilepsy or any other contraindication for receiving neurostimulation with TMS (e.g., intracranial magnetic implant, cardiac pacemaker)

Sponsors & Collaborators

• Instituto de investigación e innovación biomédica de Cádiz: lead
• Ministry of Science and Innovation, Spain: collaborator
• Andalusian Ministry of Health and Families: collaborator
• Andalusian Ministry of University, Research and Innovation: collaborator
• University of Cadiz: collaborator
• Hospital Universitario Puerta del Mar: collaborator

Study Sites (1)

Hospital Universitario Puerta del Mar

Cadiz, Cadiz, 11009, Spain

Location

Related Publications (1)

• Rashid-Lopez R, Macias-Garcia P, Cruz-Gomez AJ, Cano-Cano F, Sanchez-Fernandez FL, Sarrias-Arrabal E, Del Marco A, Gonzalez-Moraleda A, Lozano-Soto E, Sanmartino F, Espinosa-Rosso R, Gonzalez-Rosa JJ. Plasticity-Induced Motor Recovery of Bilateral Intermittent Theta Burst Stimulation in Parkinson's Disease: A Randomized, Double-Blind, Sham-Controlled, Crossover Trial. Neurol Ther. 2026 Feb;15(1):345-366. doi: 10.1007/s40120-025-00865-0. Epub 2025 Dec 6.

  PMID: 41351806 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Javier J. Gonzalez-Rosa, PhD

  University of Cadiz & Institute of Biomedical Research Cadiz (INiBICA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The patient and the examiner who administered the clinical scales and all assessments were blind to the type of iTBS delivered, which was applied by another blinded experimenter.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each patient received both active and sham iTBS in randomized order in two different sessions, separated by at least 3 months. All patients will be tested four times: at baseline (pre-stimulation) and after iTBS (post-stimulation), both for active and sham iTBS. In each session, motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment, evaluation of M1 excitability, combined structural MRI and resting-state EEG and fMRI, and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.

Study Record Dates

• First Submitted: September 2, 2023
• First Posted: February 21, 2025
• Study Start: June 1, 2022
• Primary Completion: February 12, 2024
• Study Completion: April 12, 2024
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Once the main results of the study have been published
• Access Criteria: The anonymized raw data analyzed in the present study are available on reasonable request.

Locations

ES (1)