UMIN-CTR Clinical Trial

Basic information
Public title	A sham-controlled, double-blind, parallel-group, randomized trial of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder, followed by a semi-crossover open trial of rTMS.
Acronym	A sham-controlled, double-blind, parallel-group, randomized trial of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder.
Scientific Title	A sham-controlled, double-blind, parallel-group, randomized trial of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder, followed by a semi-crossover open trial of rTMS.
Scientific Title:Acronym	A sham-controlled, double-blind, parallel-group, randomized trial of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder.
Region	Japan

Condition
Condition	Major depressive disorder (Monopolar depression)
Classification by specialty	Psychiatry
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	A main purpose of this clinical trial is to evaluate safety and efficacy, including antidepressant effect and prefrontal cognitive enhancement, of rTMS applied to medication-resistant major depression, compared with sham-control group. Moreover, rTMS-induced alterations are longitudinally investigated using MRI, EEG, and heart rate variability (vagal function). Furthermore, two different protocols of rTMS (high and low frequency rTMS) are compared in terms of safety, efficacy, and neurobiological changes.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase III

Assessment
Primary outcomes	1) Hamilton Depression Rating Scale (Ham-D) 17items and 24items: weekly evaluation 2) rTMS side effects questionnaire, which was translated in Japanese from original version of Center for Noninvasive Brain Stimulation, Harvard Medical School.: evaluated every rTMS session
Key secondary outcomes	3) Beck Depression Inventry II (BDI-II): weekly evaluation 4) State-Trait Anxiety Inventory (STAI): weekly evaluation 5) Neuropsychological Testings (Verbal Fluency Test; VFT, Wisconsin Card Sorting Test; WCST, Color Stroop Test; CST, Trail Making Test; TMT): biweekly evaluation

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Device,equipment
Interventions/Control_1	Navigation-guided high-frequency rTMS TMS coil: air-cooled figure-of-eight coil site: left dorsolateral prefrontal cortex (lt.DLPFC) frequency: 10Hz (4sec. train, 26sec. interval) intensity: 100% resting motor threshold (RMT) number of pulses: 2000pulses/session time of session: 25 minutes number of sessions: 20 to 30 sessions (4 to 6 weeks) others: concomitant application of electric pulses over left forehead synchronized with TMS pulses for high-quality sham condition
Interventions/Control_2	Navigation-guided low-frequency rTMS TMS coil: air-cooled figure-of-eight coil site: right dorsolateral prefrontal cortex (rt.DLPFC) frequency: 1Hz intensity: 100% resting motor threshold (RMT) number of pulses: 2000pulses/session time of session: 33 minutes number of sessions: 20 to 30 sessions (4 to 6 weeks) others: concomitant application of electric pulses over right forehead synchronized with TMS pulses for high-quality sham condition
Interventions/Control_3	Navigation-guided high-frequency sham rTMS TMS coil: air-cooled sham coil (figure-of-eight) site: left dorsolateral prefrontal cortex (lt.DLPFC) frequency: 10Hz (4sec. train, 26sec. interval) intensity: 60% maximum machine output number of pulses: 2000pulses/session time of session: 25 minutes number of sessions: 20 to 30 sessions (4 to 6 weeks) others: concomitant application of electric pulses over left forehead synchronized with TMS pulses for high-quality sham condition
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Aged 20-75 years-old, male and female, inpatients, self-sustained ADL 2. Capability of informed consent 3. DSM-IV-TR diagnosis of major depressive disorder, single episode (296.2x) or recurrent (296.3x) 4. Current episode duration: more than 8 weeks and less than 5 years 5. Hamilton Scale for Depression 17-item score: more than 14 6. Medication resistance (insufficient clinical benefit to more than 2 medication trials) or medication intolerance (intolerant to more than 2 medication trials) during current episode
Key exclusion criteria	1. Absolute contraindications of rTMS (inplanted medical devices or intracranial ferromagnetic material) 2. Relative contraindications of rTMS, including a) pregnancy, b) seizure disorders or paroxysmal EEG abnormality, and c) medications known to lower seizure threshold 3. Other current Axis I disorders 4. Suicidality (Ham-D suicidality score more than 3) 5. Psychotic features during current episode 6. Instability of physical conditions 7. History of neurologic disorders 8. Previous treatments with rTMS and VNS, and treatment history of ECT within a year
Target sample size	90

Research contact person
Name of lead principal investigator	1st name Motoaki Middle name Last name Nakamura
Organization	Kinkou Hospital, Kanagawa Psychiatric Center
Division name	Laboratory of Neuromodulation
Zip code	233-0006
Address	2-5-1, Serigaya, Kounan-ku, Yokohama, Kanagawa, Japan
TEL	045-822-0241
Email	motoaki@motoaki.com

Public contact
Name of contact person	1st name Motoaki Middle name Last name Nakamura
Organization	Kinkou Hospital, Kanagawa Psychiatric Center
Division name	Laboratory of Neuromodulation
Zip code	233-0006
Address	2-5-1, Serigaya, Kounan-ku, Yokohama, Kanagawa, Japan
TEL	045-822-0241
Homepage URL	http://www.kinkou.org/rTMS.html
Email	motoaki@motoaki.com

Sponsor
Institute	Kinkou Hospital, Kanagawa Psychiatric Center
Institute
Department

Funding Source
Organization	Ministry of Education, Culture, Sports, Science and Technology
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	IRB, Kanagawa Psychiatric Center
Address	2-5-1, Serigaya, Kounan-ku, Yokohama, Kanagawa, Japan
Tel	045-822-0241
Email	asai.20031@kanagawa-pho.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2012 Year 04 Month 23 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2011 Year 11 Month 27 Day
Date of IRB	2011 Year 11 Month 29 Day
Anticipated trial start date	2012 Year 05 Month 01 Day
Last follow-up date	2019 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2012 Year 04 Month 20 Day
Last modified on	2020 Year 04 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000009167