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Double blinded study of high frequency repetitive transcranial magnetic stimulator for Parkinson's disease. (rTMS treatment study of Parkinson's disease)

Double blinded study of high frequency repetitive transcranial magnetic stimulator for Parkinson's disease.

No significant difference in the rate of adverse event occurrence between real and sham stimulation group was observed. No serious adverse events related to the high frequency repetitive transcranial magnetic stimulator were reported in this study.

Primary outcome Changes in UPDRS Part III (motor symptoms) total score at drug-on stage from the baseline score (mean (SD)) were -5.3 (6.3) for real stimulation group and -4.0 (5.2) for sham stimulation group. No significant difference between real and sham group was observed for improvement in the score. Secondary outcomes No significant difference between real and sham stimulation group was observed for improvement in any of the secondary outcomes.

The safety of the rTMS treatment for Parkinson's disease has been confirmed. However, the efficacy of the rTMS treatment for motor symptoms and non-motor symptoms was not proven in this study.

https://www.neurology-jp.org/neuro2018/program/pdf/18.pdf

Yoshikazu Ugawa

Fukushima Medical University School of Medicine

1 Hikarigaoka, Fukushima, 960-1295

ugawatky@umin.net

Masahiro Echigo

Nihon Kohden Corporation

11-2, Kusunokidai 1-chome, Tokorozawa, Saitama

+81-3-5996-8156

Masahiro_Echigo@mb1.nkc.co.jp

COMPLETED

Feb. 02, 2015

Interventional

Multicenter, randomized and double blinded comparison study with sham control.

double blind

Yes

3

Eligible patients are expected to meet all of the following criteria:
(1) PD patients diagnosed as Idiopathic PD based on the criteria of UK Parkinson's Disease Society brain bank
(2) PD patients whose symptoms are not considerably improved with L-dopa and/or dopamine agonist treatments, and also are at stage 2 to 4 in the modified Hoehn-Yahr Scale
(3) Patients who have been receiving a stable dosage of L-dopa and/or dopamine agonist at regular intervals for 4 weeks before rTMS treatment
(4) Patients who have been receiving a stable dosage of anticholinergic drugs, selegiline, entacapone, amantadine hydrochloride, droxidopa, zonisamide or istradefylline at regular intervals for 4 weeks before rTMS treatment
(5) Patients 20 years and older at time of providing informed consent
(6) In-patients or out-patients who can come to the hospitals where the study is conducted
(7) Patients who have voluntarily provided written consent for participation in this study, based on complete understanding our full explanation

Patients meeting any of the following criteria are ineligible for this study:
(1) Patients exhibiting severe psychiatric symptoms such as severe hallucinations, delusion, confusion, abnormal behavior and so on, within 6 months (26 weeks) before the initiation of rTMS treatment
(2) Patients with drug or alcohol addiction (by ICD10 classification)
(3) Patients with less than a 24 score in mini-mental state examination at a screening
(4) Patients with less than a 11 score in UPDRS Part III at a screening
(5) Patients having a history of receiving surgical treatments (such as deep brain stimulation)
(6) Patients having taken medication listed below within 4 weeks of the initiation of rTMS treatment
+ dopamine receptor antagonistic antipsychotics (e.g. phenothiazines, butyrophenones, benzamides)
+ dopamine receptor antagonistic cardiovascular drugs (e.g. reserpine)
(7) Patients taking medication listed below currently or having taken it within 1 week of the initiation of rTMS treatment.
+ dopamine receptor antagonistic gastrointestinal drugs (e.g. metoclopramide and sulpiride, except for domperidone)
(8) Patients who have previously received rTMS treatment
(9) Patients with metal implants (e.g. clips, metals, and cochlear implant) in the head (except for oral implants)
(10) Patients having a cardiac pacemaker, implantable cardioverter defibrillators (ICD), vagal nerve stimulator or implantable drug infusion pump
(11) Patients with a large cerebral infarction, cerebral trauma, brain tumor, or epilepsy
(12) Patients having a malignant tumor, severe hepatic, renal, hematologic, respiratory, gastrointestinal or cardiovascular disease or metabolic or electrolyte imbalance. (Patients having a history of malignant tumors but being free of relapse for more than 5 years are allowed to be included. Severity criteria are based on grade 4 in Common Terminology Criteria for Adverse Events (CTCAE) v4.0.)
(13) Patients in whom no motor evoked potentials were elicited from the tibialis anterior muscle by TMS at the maximum stimulator output
(14) Patients who participated in other trials within 12 weeks before the date of providing informed consent for this study
(15) Pregnant patients or patients having a possibility of pregnancy. Patients who are breast feeding or attempting to become pregnant.
(16) Patients who were judged as ineligible by the principle investigator or subinvestigator

Both

Parkinson's disease patients

Intervention type:DEVICE Name of intervention:High frequency transcranial magnetic stimulator SMN-NX Dose form / Japanese Medical Device Nomenclature:DEVICE Repetitive transcranial magnetic stimulator Route of administration / Site of application:PERCUTANEOUS Dose per administration: Dosing frequency / Frequency of use:QW Planned duration of intervention:8 weeks Intended dose regimen:One intervention session consists of 20 trains. One train consists of 50 pulses at 5 Hz for 10 seconds. In one session, 20 trains are repeated once in one minute for 20 minutes. In total, 1000 TMS pulses are given in one intervention. detailes of teratment arms:Subjects are PD patients who have some daily problems even with best L-dopa and/or dopamine agonist treatments. Comparative intervention name:Sham stimulation Dose form / Japanese Medical Device Nomenclature:DEVICE Electric stimulator Route of administration / Site of application:PERCUTANEOUS Dose per administration: Dosing frequency / Frequency of use:QW Planned duration of intervention:8 weeks Intended dose regimen:Click noise and electric current on scalp, both of which synchronized to magnetic stimulation. Current stimulation with the intensity fixed at two times sensory threshold.

Changes in UPDRS Part III (motor symptoms) total score at drug-on stage from the baseline score.

1) Time course of modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Part I to IV, total)
2) Time course of self-assessed daily activity (Visual analog scale)
3) Time course of averaged duration of off period in a day
4) Changes in dropouts due to increasing or addition of anti-Parkinsonian drugs as a result of worsening of motor symptoms.

May. 08, 2015