ANZCTR - Registration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12626000783325

Ethics application status

Approved

Date submitted

19/06/2026

Date registered

30/06/2026

Date last updated

29/09/2026

Date data sharing statement initially provided

30/06/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

Personalised combined transcranial magnetic and electrical stimulation in healthy adults

Scientific title

Investigating the effects of individualised frequency phase-synchronised iTBS-tACS in healthy participants

Additional trial identifiers [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Related trial records

Health condition

Health condition(s) studied:

Depression

Condition category

Condition code

Mental Health

Depression

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

In a randomised, single-blind, crossover design, participants will complete three experimental sessions, with at least 5 days between sessions. During each session, participants will receive one of three stimulation conditions: (1) individualised-frequency phase-synchronised intermittent theta burst stimulation combined with transcranial alternating current stimulation (iTBS-tACS), (2) fixed-frequency phase-synchronised iTBS-tACS, or (3) sham iTBS-tACS.

iTBS-tACS is a non-invasive brain stimulation intervention that combines transcranial magnetic and electrical stimulation to modulate brain activity. iTBS will be delivered using a Neuro-MS/D TMS device (Neurosoft, Russia) with a cooled figure-of-eight coil. tACS will be delivered via a RIO Transceiver system (eemagine Medical Imaging Solutions GmbH, Germany). Stimulation will be delivered over the left dorsolateral prefrontal cortex (DLPFC). iTBS (600 pulses per session) will be delivered at 80% of resting motor threshold. tACS will be delivered at an intensity of up to 1-2 mA (peak-to-peak). In both active conditions, iTBS and tACS will be delivered in a phase-synchronised manner to maintain a predefined phase relationship between the two forms of stimulation. Each session will consist of a single stimulation lasting approximately 4 minutes.

Frequency/duration of intervention: 1 × 4-minute stimulation session per visit, across 3 visits in total (one session under each of the three stimulation conditions), with a minimum of 5 days between visits.

In the fixed-frequency condition, stimulation will be delivered using conventional frequencies of 5 Hz (theta) and 50 Hz (gamma). In the individualised-frequency condition, theta and gamma stimulation frequencies will be determined based on oscillatory activity recorded by electroencephalography (EEG) during a working memory task prior stimulation. This individualisation is based on evidence suggesting that matching stimulation frequencies with endogenous neural oscillations may improve neuromodulatory efficacy.

The intervention will be delivered face-to-face on an individual basis by trained research team experienced in non-invasive brain stimulation. All study procedures will be conducted at John Curtin School of Medical Research, Australian National University, Canberra, Australia. The intervention will be delivered face-to-face on an individual basis by trained research team experienced in non-invasive brain stimulation. All study procedures will be conducted at John Curtin School of Medical Research, The Australian National University, Canberra, Australia. Attendance will be recorded for all study visits. Stimulation parameters will be documented by the research team during each session. Participants will receive reminders prior to each visit to support adherence.

Intervention code [1]

Treatment: Devices

Description of the comparator or control

Sham iTBS-tACS will be delivered using the same devices and electrode/coil placement as active conditions, with sham settings that mimic the sensory experience of stimulation without delivering effective neuromodulatory current or magnetic pulses.

Specifically, for sham tACS, the same device will be used, with effective stimulation delivered only briefly (approximately 2 seconds) to mimic the skin sensations (e.g. tingling and itching) associated with active tACS, without producing effective physiological effects. For sham iTBS, the coil will be positioned vertically (90° to the scalp) to produce pressure, vibration, and clicking sounds similar to those of active stimulation, without delivering effective stimulation to the brain.

These sham stimulation will follow the same session structure and duration as active conditions (approximately 4 minutes per session).

Control group

Placebo

Outcomes

Primary outcome [1]

Physiological: Change in TMS-evoked potentials (TEPs)

Timepoint [1]

Baseline, 0–30 minutes post-stimulation (primary outcome timepoint) and 30–60 minutes post-stimulation at each visit.

Secondary outcome [1]

Physiological: Change in oscillatory power (e.g., theta power)

Timepoint [1]

Baseline, 0–30 minutes post-stimulation and 30–60 minutes post-stimulation at each visit.

Secondary outcome [2]

Physiological: frontoparietal connectivity

Timepoint [2]

Baseline, 0–30 minutes post-stimulation and 30–60 minutes post-stimulation at each visit.

Secondary outcome [3]

Behavioural: Change in working memory performance

Timepoint [3]

Baseline, 0–30 minutes post-stimulation and 30–60 minutes post-stimulation at each visit.

Secondary outcome [4]

Behavioural: Change in mood

Timepoint [4]

Baseline and post-stimulation at each visit.

Eligibility

Key inclusion criteria

i. Aged between 18 and 65.
ii. No active medical illness.
iii. No current psychiatric illness or a history of a psychotic disorder or bipolar disorder.
iv. Able to provide informed consent.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Healthy volunteers

Yes

Key exclusion criteria

i. Fails TMS and tACS safety screening (e.g., says ‘yes’ to having a metal implant in head).
ii. Pregnant or breastfeeding.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a randomisation table created by a computer software. All participants will receive all three stimulation conditions, however the order of the conditions will be randomly assigned for each participant (i..e Participant A may receive stimulation condition 3 followed by 1 and then 2).

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Crossover

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Sample size was calculated in G*Power using a repeated-measures ANOVA based on the primary comparison of interest (individualised frequency condition vs. fixed frequency condition), which was modelled as a two-level within-subject factor, with the TEPs measured by TMS-EEG as the primary outcome measure. As no previous studies have directly compared these specific stimulation conditions, and given inherent variability of TMS-EEG measures, a conservative effect size (f) of 0.20 was assumed, along with an alpha level of 0.05, statistical power of 0.80, and a correlation of 0.75 between repeated measures. This yielded 27 participants. 30 will be recruited to account for approximately 10% data loss.

Repeated measures ANOVAs and cluster-based permutation statistics will be used to compare neurophysiological outcomes (TEPs, oscillatory power, frontoparietal connectivity) across the three stimulation conditions. Secondary analyses will also include correlations between neurophysiological and behavioural outcomes.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

31/07/2026

Actual

10/09/2026

Date of last participant enrolment

Anticipated

1/04/2027

Actual

Date of last data collection

Anticipated

19/04/2027

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

ACT

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Australian Government Research Training Program Scholarship

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

The Australian National University

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

ACT Health Human Research Ethics Committee

Ethics committee address [1]

https://health.act.gov.au/act-health-system/research-data-and-publications/research/research-ethics-and-governance

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/01/2026

Approval date [1]

20/04/2026

Ethics approval number [1]

2026.ETH.00014

Summary

Brief summary

Depression is one of the leading causes of disability worldwide. Intermittent theta burst stimulation (iTBS) is a safe and effective neuromodulation therapy for depression, but its effects can vary between individuals. This study aims to investigate whether combining iTBS with transcranial alternating current stimulation (tACS) using a personalised, phase-synchronised approach improves brain responses compared with fixed-frequency and sham stimulation. The main hypothesis is that individualising stimulation frequencies based on brain activity will enhance the effects on brain function, compared with fixed-frequency and sham conditions. The findings will help inform the development of more effective, personalised brain stimulation treatments for depression in future research.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Paul Fitzgerald

Address

Room 1.27, Florey Building, 54 Mills Road, The Australian National University, Canberra ACT 2601

Country

Australia

Phone

+61 2 6125 2622

Fax

[email protected]

Contact person for public queries

Name

Jiaxi Huang

Address

Room 2.32, Florey Building, 54 Mills Road, The Australian National University, Canberra ACT 2601

Country

Australia

Phone

+61439131825

Fax

[email protected]

Contact person for scientific queries

Name

Jiaxi Huang

Address

Room 2.32, Florey Building, 54 Mills Road, The Australian National University, Canberra ACT 2601

Country

Australia

Phone

+61439131825

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

No
No IPD sharing reason/comment: No, IPD will not be available.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically