Standardization and Optimization of TMS Protocols for the Treatment of PD With Depression or Cognitive Impairment

Guangdong Provincial People's Hospital (Guangdong Provincial Academy of Medical Sciences)

Status: Unknown

Conditions: TMS Protocols in the Treatment of PD

Treatments: Device: repetitive transcranial magnetic stimulation(rTMS)

Study type: Interventional

Funder types: Other

Identifiers

NCT03552861

GDREC2017083H（R1）

Details and patient eligibility

About

The goal of this study is to determine whether transcranial magnetic stimulation (TMS) is an effective treatment in Parkinson's disease patients with depression or cognitive impairment. The study consists of seven total visits to all. Compensation will be provided for each visit.

Full description

Transcranial magnetic stimulation(TMS) is a valuable non-invasive brain stimulation tool for interventional neurophysiology applications, which generate local current and modulates brain activity in a specific, cortico-subcortical network. Repetitive TMS (rTMS) is developed as it is safe and well-tolerated. The left dorsolateral prefrontal cortex (DLPFC) high-frequency rTMS treatment has been proved effective for depression by many clinical studies,as well as the low-frequency rTMS over the right DLPFC. In Europe, guidelines on the therapeutic use of rTMS was published in 2014, in which they pointed out that high-frequency rTMS over left DLPFC could be used as therapeutic method for dPD, with a B-level recommendation. Among several small and pilot studies of rTMS in PD patients, rTMS over either the motor cortex or DLPFC has been reported to show beneficial effects on cognitive impairment with no serious adverse events.However, the relative effectiveness of rTMS over left or right prefrontal, or both regions on both depression and cognitive impairment symptoms, has yet to be established in PD patients.

The investigators propose to conduct a ten-center, blinded, sham-controlled, randomized, parallel-group study of fixed-dose, high-frequency and/or low-frequency rTMS in 252 PD patients who are experiencing depressive symptoms or cognitive impairment. Subjects will be randomized to receive rTMS over right and left DLPFC, both or neither active/sham rTMS. Subjects will receive rTMS for 45 minutes treatment over a 2-week period, all subjects will undergo a comprehensive assessment of mood, cognition, motor and quality of life before and after the last rTMS treatment, and after 2,4 and 12 weeks post-treatment. This study directly addresses the expansion of rTMS as an alternative treatment for depression and cognitive impairment in the PD population.

Enrollment: 252 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years old and ≤ 80 years old, male or female
2. Subjects with idiopathic PD (according to Movement Disorder Society Clinical Diagnostic Criteria，both clinically established PD and clinically probable PD)
3. Subjects fulfilling the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition(DSM-IV)
4. Did not use antidepressant(s) for a minimum of 2 months
5. Untreated or had stabilized doses of anti-Parkinson's disease medication for > 28 days, and maintain this dose during treatment
6. Subjects or their legal representatives could follow the research plan, visit plan
7. Subjects or their legal guardians agree to participate in the trial and signs informed consent

Exclusion criteria

1. Subjects with Parkinson's plus syndrome(PPS) or Secondary Parkinson Disease caused by vascular factors, toxins, and drugs
2. Subjects with persistent head tremor
3. Subjects with dementia
4. Subjects with suicidal tendency and psychotic symptoms
5. Subjects with consciousness, history of stroke, severe neurological/psychiatric disorders such as transient ischemic attack within 1 year prior to screening (Visit 1), or other severe organic diseases
6. Accepted deep brain stimulation(DBS) or other invasive brain surgery previously
7. Subjects with contraindications for repetitive transcranial magnetic stimulation(rTMS), such as history of epileptic seizures, pregnant, implantation of pacemaker or other metal implants in the body, intracranial hypertension, severe hemorrhagic tendency, etc.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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252 participants in 4 patient groups

left and right DLPFC active treatment

Active Comparator group

Description:

Intervention: repetitive transcranial stimulation (rTMS) Each patient will be given 5 treatment sessions per week for 2 weeks (a total of 10 sessions).In each rTMS conditioning session,1200 pulses of stimuli at an intensity of 100% rest motor threshold (RMT) will give over the left and rigt DLPFC.Each session is 45 minutes long and will be consisted of 10Hz stimulation trains (active) over the left DLPFC and 1Hz over the right DLPFC，Interval of 5 minutes each side.During rTMS blocks, the coil will be oriented tangential to the surface.

Treatment:

Device: repetitive transcranial magnetic stimulation(rTMS)

left DLPFC active and right DLPFC sham treatment group

Active Comparator group

Description:

Each patient will be given 5 treatment sessions per week for 2 weeks (a total of 10 sessions).In each rTMS conditioning session,1200 pulses of stimuli at an intensity of 100% rest motor threshold (RMT) will give over the left and rigt DLPFC.Each session is 45 minutes long and will be consisted of 10Hz stimulation trains (active) over the left DLPFC and 1Hz over the right DLPFC，Interval of 5 minutes each side.During rTMS blocks, the coil will be oriented tangential to the surface. For sham control rTMS blocks, the coil will be oriented 90◦ away from the scalp so that no pulses perturbed underlying neural tissue.

Treatment:

Device: repetitive transcranial magnetic stimulation(rTMS)

left DLPFC sham and right DLPFC active treatment group

Active Comparator group

Description:

Each patient will be given 5 treatment sessions per week for 2 weeks (a total of 10 sessions).In each rTMS conditioning session,1200 pulses of stimuli at an intensity of 100% rest motor threshold (RMT) will give over the left and rigt DLPFC.Each session is 45 minutes long and will be consisted of 10Hz stimulation trains (active) over the left DLPFC and 1Hz over the right DLPFC，Interval of 5 minutes each side.During rTMS blocks, the coil will be oriented tangential to the surface. For sham control rTMS blocks, the coil will be oriented 90◦ away from the scalp so that no pulses perturbed underlying neural tissue.

Treatment:

Device: repetitive transcranial magnetic stimulation(rTMS)

left DLPFC sham and right DLPFC sham treatment group

Sham Comparator group

Description:

Each patient will be given 5 treatment sessions per week for 2 weeks (a total of 10 sessions).In each rTMS conditioning session,1200 pulses of stimuli at an intensity of 100% rest motor threshold (RMT) will give over the left and rigt DLPFC.Each session is 45 minutes long and will be consisted of 10Hz stimulation trains (active) over the left DLPFC and 1Hz over the right DLPFC，Interval of 5 minutes each side.During rTMS blocks,the coil will be oriented 90◦ away from the scalp so that no pulses perturbed underlying neural tissue.

Treatment:

Device: repetitive transcranial magnetic stimulation(rTMS)