Clinical trial NCT03552861: Standardization and Optimization of TMS Protocols for the Treatment of PD With Depression or Cognitive Impairment
Official title: Standardization and Optimization of TMS Protocols for the Treatment of Early and Mild-to-late Stage Parkinson's Disease With Depression or Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: TMS Protocols in the Treatment of PD
Keywords: Parkinson's disease
rTMS
Dorsal prefrontal cortex
Depression
Cognitive impairment
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2018-06-12
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hamilton Depression Scale（HAMD）
timeFrame: 3 months
measure: Beck Depression Inventory（BDI）
timeFrame: 3 months
Secondary outcomes:
measure: Mini-mental State Examination（MMSE）
timeFrame: 3 months
measure: Montreal Cognitive Assessment Scale（MoCA）
timeFrame: 3 months
measure: Named test of the Aphasia Battery of Chinese
timeFrame: 3 months
measure: Similarity test
timeFrame: 3 months
measure: Symbol Digit modalities test（SDMT）
timeFrame: 3 months
measure: Verbal fluency test（VFT）
timeFrame: 3 months
measure: Logical memory test（LMT）
timeFrame: 3 months
measure: Delayed memory test（DMT）
timeFrame: 3 months
measure: Digit span test（DST）
timeFrame: 3 months
measure: Ten point clock test
timeFrame: 3 months
measure: Uniform Parkinson's Disease Rating Scale Ⅲ（UPDRSⅢ）
timeFrame: 3 months
measure: Modified Hoehn & Yahr scale（H-Y）
timeFrame: 3 months
measure: Time up and go test（TUG test）
timeFrame: 3 months
measure: Activity of Daily Living Scale（ADL）
timeFrame: 3 months
measure: Parkinson's Disease Questionnaire（PDQ-39）
timeFrame: 3 months
measure: Non-motor symptoms questionnaire(NMS-Q)
timeFrame: 3 months
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 3 months
measure: Hamilton Anxiety Scale（HAMA）
timeFrame: 3 months
measure: Beck Anxiety Inventory（BAI）
timeFrame: 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Fuzhou
country: China
facility: Affiliated Union Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Shenyang
country: China
facility: First Affiliated Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Lijuan Wang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brys M, Fox MD, Agarwal S, Biagioni M, Dacpano G, Kumar P, Pirraglia E, Chen R, Wu A, Fernandez H, Wagle Shukla A, Lou JS, Gray Z, Simon DK, Di Rocco A, Pascual-Leone A. Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial. Neurology. 2016 Nov 1;87(18):1907-1915. doi: 10.1212/WNL.0000000000003279. Epub 2016 Oct 5.
citation: Kojovic M, Kassavetis P, Bologna M, Parees I, Rubio-Agusti I, Berardelli A, Edwards MJ, Rothwell JC, Bhatia KP. Transcranial magnetic stimulation follow-up study in early Parkinson's disease: A decline in compensation with disease progression? Mov Disord. 2015 Jul;30(8):1098-106. doi: 10.1002/mds.26167. Epub 2015 Mar 5.
citation: Dagan M, Herman T, Mirelman A, Giladi N, Hausdorff JM. The role of the prefrontal cortex in freezing of gait in Parkinson's disease: insights from a deep repetitive transcranial magnetic stimulation exploratory study. Exp Brain Res. 2017 Aug;235(8):2463-2472. doi: 10.1007/s00221-017-4981-9. Epub 2017 May 16.