prTMS as an Intervention for Bradykinesia in Parkinson's Disease (ADAPT-BK)

Danish Research Centre for Magnetic Resonance

Status: Enrolling

Conditions: Bradykinesia; Parkinson Disease

Treatments: Device: Sham patterned repetitive transcranial magnetic stimulation (prTMS); Device: Active patterned repetitive transcranial magnetic stimulation (prTMS)

Study type: Interventional

Funder types: Other

Identifiers

NCT07397377

2500445

Details and patient eligibility

About

This study investigates the use of patterned repetitive transcranial magnetic stimulation (prTMS) as an intervention for bradykinesia in Parkinson's Disease (PD). More specifically, the study aims to determine whether prTMS over the supplementary motor area (SMA) can reduce severity of bradykinesia in PD patients. This approach may open for more targeted and effective treatment of bradykinesia in PD.

Full description

Bradykinesia is one of the core symptoms of Parkinson's Disease (PD) and has multiple facets. Movements become slower and decrease in amplitude. Speed and amplitude of movements decline gradually during repetitive movements, referred to as sequence effect. Spontaneous movements are also reduced, and movement initiation is impaired. These symptoms arise from dysfunction within the brain's motor network, particularly involving the basal ganglia-thalamo-cortical loop. The consequences of bradykinesia are far-reaching, severely affecting the patient's daily life and well-being.

Bradykinesia is primarily treated successfully with pharmacologically dopamine precursor levodopa and/or dopamine agonists. However, not all facets of bradykinesia response to dopamine such as the sequence effect and in addition as disease progresses adverse side effects emerge from medication such as dyskinesia which is involuntary choreiform or dystonic movements. These adverse effects require advanced therapies such as invasive treatment with deep brain stimulation (DBS). However, DBS is highly invasive, expensive, and may come with serious side effects.

Transcranial magnetic stimulation (TMS) has emerged as a promising non-invasive and cost-effective intervention for alleviating bradykinesia. In particular, patterned repetitive TMS (prTMS) over several brain regions including the supplementary motor area (SMA) has shown potential in modulating dysfunctional neural circuits and improving motor symptoms in patients with PD. Recent evidence suggests that the efficacy of prTMS may be enhanced by aligning stimulation with specific brain states, as the brain is most responsive to plasticity-inducing protocols right before a movement.

The current study aims to develop and validate a novel burst-based prTMS protocol called quadri-pulse stimulation (QPS), which consist of high-frequency burst with four pulses in each burst. An excitatory 200 hertz (Hz) QPS protocol has already shown to induce long-lasting plasticity changes and by incorporating the state of the brain the study aim to further enhance the effect of this QPS protocol.

Through a cross-over study design the study will apply active QPS right before a movement, active QPS between movement and sham condition before a movement in patients with PD to determine which produces a meaningful reduction in bradykinesia severity measured by Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) and Modified Bradykinesia Rating Scale (MBRS).

Enrollment: 27 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Above 18 years of age. Clinically established or probable Parkinson's Disease (PD), according to the Movement Disorder Society.

Clinical Diagnostic Criteria for PD. Stable antiparkinsonian medicine for at least four weeks. Signed informed consent.

Exclusion criteria

Psychiatric disorders. Current use of antipsychotic medication, Donepezil, or GABAergic agents (e.g., pregabalin, gabapentin).

Frequent benzodiazepine or opioid use defined as more than once per week on a regular basis.

History of neurological disease other than PD. Past or present mental illness. History of epilepsy/conditions associated with increased risk of seizure induction through transcranial magnetic stimulation (TMS).

Close relatives suffering from epilepsy/conditions associated with increased risk of seizures.

Contraindications for magnetic resonance imaging (MRI) Contraindications for TMS Female participants of childbearing age must not be pregnant and must use contraception during the trial.

Refuse to be informed about new health-related information and accidental health-related findings that might appear through participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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27 participants in 3 patient groups

Active patterned repetitive transcranial magnetic stimulation (prTMS) before a movement

Active Comparator group

Description:

Real stimulation with four pulses at the frequency of 200 Hertz (Hz) repeating a 0.2Hz will be delivered on the supplementary motor area (SMA) using the active side of the coil for 30 min. Every burst will be given 100 milliseconds (ms) before a movement.

Treatment:

Device: Active patterned repetitive transcranial magnetic stimulation (prTMS)

Active patterned repetitive transcranial magnetic stimulation (prTMS) between a movement

Experimental group

Description:

Real stimulation with four pulses at the frequency of 200 hertz (Hz) repeating a 0.2Hz will be delivered on the supplementary motor area (SMA) using the active side of the coil for 30 min. Every burst will be given between movements.

Treatment:

Device: Active patterned repetitive transcranial magnetic stimulation (prTMS)

Sham patterned repetitive transcranial magnetic stimulation (prTMS) before a movement

Sham Comparator group

Description:

Sham stimulation with four pulses at the frequency of 200 hertz (Hz) repeating a 0.2Hz will be delivered on the supplementary motor area (SMA) using the non-active side of the coil for 30 min. Every burst will be 100 milliseconds (ms) before a movement.

Treatment:

Device: Sham patterned repetitive transcranial magnetic stimulation (prTMS)