How brain functioning affects the results of transcranial magnetic stimulation treatment

ISRCTN	ISRCTN18267156
DOI	https://doi.org/10.1186/ISRCTN18267156
Secondary identifying numbers	7111

Submission date: 22/08/2025
Registration date: 28/08/2025
Last edited: 09/09/2025

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
The symptoms of depression can be complex and vary widely between people. If you're depressed, you may feel sad, hopeless and lose interest in things you used to enjoy.
Transcranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. TMS is typically used when medication hasn't been effective.
This study aims to test whether a new TMS protocol, including individual imaging-based targeting, improves outcomes in depression.

Who can participate?
Patients aged 18 to 67 years referred to the Helsinki University Central Hospital for rTMS for major depressive disorder (MDD)

What does the study involve?
The study involves a 2-hour visit to Aalto University Advanced Magnetic Imaging Centre for magnetic resonance imaging (MRI). This is followed by a 1-2-hour meeting including definition of dose and possible targets for the treatment. A nurse uses a randomized list to select the protocol, and the participants and the researchers who evaluate the outcome will not know the method. TMS is delivered five times a week for up to 20 sessions and combined with brief cognitive tasks and questionnaires.

What are the possible benefits and risks of participating?
Possible benefits of the study include improved outcomes of rTMS treatment and risks resemble those of usual TMS treatment, including uncomfortable stimulation site sensations and a small risk of seizure.

Where is the study run from?
Helsinki University Central Hospital Department of Psychiatry (Finland)

When is the study starting and how long is it expected to run for?
January 2023 to May 2028

Who is funding the study?
1. Research Council of Finland
2. Finnish government funding for health care research
3. Helsinki and Uusimaa Hospital District

Who is the main contact?
Dr Tuukka Raij, tuukka.raij@hus.fi

Contact information

Dr Tuukka Raij
Public, Scientific, Principal Investigator

Valskarinkatu 12
PO Box 590
Helsinki
00290 HUS
Finland

ORCID ID	0000-0002-9834-5570
Phone	+358 (0)504285473
Email	tuukka.raij@hus.fi

Study information

Study design	Interventional double-blind randomized controlled trial
Primary study design	Interventional
Secondary study design	Randomised parallel trial
Study setting(s)	Hospital
Study type	Treatment, Efficacy
Participant information sheet	Not available in web format, please use the contact details to request a participant information sheet
Scientific title	Effect of cognition and target model optimization on outcome of Helsinki individual transcranial magnetic stimulation treatment
Study acronym	HIT3
Study objectives	New protocol results in better outcome than regular transcranial magnetic stimulation (TMS)
Ethics approval(s)	Approved 25/06/2025, HUS regional medical research ethics committee (HUS Keskuskirjaamo, Helsinki, PO Box 200, Finland; +358 (0)403594618; eettiset.toimikunnat@hus.fi), ref: HUS/12135/2022
Health condition(s) or problem(s) studied	Major depressive disorder, resistant to at least two antidepressants
Intervention	Participants are randomized 1:1 to receive transcranial magnetic theta burst stimulation with: 1. Regular theta burst protocol 2. New protocol including individually planned targeting Each group is further divided 1:1 to a cognitive priming task or no task. The research nurse who delivers treatment uses balanced lists for randomization, while researchers who evaluate the outcome and the patient remain blind to the treatment arm. Theta burst stimuli are delivered at 120% (or nearest tolerated) of motor threshold five times a week for 20 days.
Intervention type	Device
Pharmaceutical study type(s)	Not Applicable
Phase	Phase III
Drug / device / biological / vaccine name(s)	Transcranial magnetic stimulation
Primary outcome measure	Severity of depression measured using the Montgomery Åsberg Depression Rating Scale (MADRS) rated before and within 2 weeks after treatment
Secondary outcome measures	1. Functioning measured using the Social and Occupational Functioning Scale (SOFAS) before and within 2 weeks after treatment 2. Severity of depression measured using the self-evaluated Patient health questionnaire (PHQ-9) before and within 2 weeks after treatment and 6 weeks after treatment 3. Remission defined as MADRS <11 within 2 weeks after treatment 4. Response defined as MADRS within 2 weeks after treatment >50 % less than MADRS before treatment
Overall study start date	01/01/2023
Completion date	31/05/2028

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	67 Years
Sex	Both
Target number of participants	Independent data monitoring group conducts interim analysis at n = 40 with stopping rules p <0.005 or a new power calculation suggesting power <80 % to detect group difference with p <0.048 with n = 80
Key inclusion criteria	1. Diagnosis of major depressive disorder (DSM-IV) as the principal diagnosis with Patient Health Questionnaire-9 score >14 2. Inability to tolerate antidepressant medication or unresponsiveness to minimum of 2 months trial with adequate dose of antidepressant 3. No change in antidepressive medication in 4 weeks prior to treatment
Key exclusion criteria	1. Previous rTMS treatment 2. Borderline personality features exceeding 7 points in McLean Screening Instrument for Borderline Personality Disorder, or other somatic or psychiatric conditions that likely interfere with recovery from depression with TMS (an unstable medical illness, substantial neurological illness, chronic pain, psychotic disorder or current psychotic symptoms, substance abuse or dependency within last 3 months, >2 mg lorazepine equivalents benzodiazepine use daily or any anticonvulsant, or lifetime history of non-response to an adequate course - i.e., a minimum of eight treatments - of electroconvulsive therapy) 3. Patients with safety risks including active suicidality, pregnancy, magnetic metal or leads in the upper body, or history of seizures
Date of first enrolment	15/09/2025
Date of final enrolment	31/12/2027

Locations

Countries of recruitment

Finland

Study participating centre

Helsinki University Central Hospital Department of Psychiatry

Valskarinkatu 12
PO Box 590
Helsinki
00029 HUS
Finland

Sponsor information

Hospital District of Helsinki and Uusimaa
Hospital/treatment centre

Välskärinkatu 12
PO Box 590
Helsinki
00029 HUS
Finland

Phone	+358 (0)406127001
Email	pia.virtanen@hus.fi
Website	https://www.helsinki.fi/fi/laaketieteellinen-tiedekunta/tutkimus/tieteenalat/psykiatrian-osasto
"ROR"	https://ror.org/020cpqb94

Funders

Funder type

Government

Research Council of Finland
Government organisation / Universities (academic only)

Alternative name(s): Suomen Akatemia, Finlands Akademi, Academy of Finland, AKA
Location: Finland

Helsinki and Uusimaa Hospital District

No information available

Government of Finland

No information available

Results and Publications

Intention to publish date	31/12/2028
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	Planned publication in a peer-reviewed journal
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available due to the need to protect privacy of the participants.

Editorial Notes

09/09/2025: Ethics approval details added.
22/08/2025: Study's existence confirmed by HUS regional medical research ethics committee.