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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12625001264471
Ethics application status
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Approved
Date submitted
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29/10/2025
Date registered
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14/11/2025
Date last updated
Help: Date last updated
14/11/2025
Date data sharing statement initially provided
Help: Data sharing statement date
14/11/2025
Type of registration
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Prospectively registered

Titles & IDs
Public title
Exploring the Effect of a Brain Stimulation Approach on Brain Activity and Connectivity in Adults with Anxiety and Depression
Scientific title
Effect of High Definition transcranial Infraslow Grey Noise Triple Network Neuromodulation (HD-tIGN-TNN) on cortical activity and functional connectivity for Internalizing Psychopathology in Adults: A Proof-of-Concept Study
Additional trial identifiers [1] 315402 0
None
Universal Trial Number (UTN)
Trial acronym
Related trial records
This study is a sub-study of the proof-of-concept trial investigating the safety and effectivity of HD-tIGNS-TNN compared to sham stimulation, as measured by the change in anxiety and/or depression symptom severity from baseline to mid-intervention or immediately post-intervention in individuals with clinically diagnosed depression and/or anxiety. The trial is registered in clinical trials registry: ACTRN12625000862448

Health condition
Health condition(s) studied:
Anxiety disorders 338909 0
Depressive disorders 338910 0
Condition category
Condition code
Mental Health 335206 335206 0 0
Anxiety
Mental Health 335207 335207 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
For the active stimulation group, the HD-tIGN-TNN will be delivered by a researcher with experience in delivering neuromodulation techniques, for a single session of 30min with 60s ramp up and ramp down at the beginning and end, with continuous stimulation in between. The gray noise (50%) will be superimposed on the infraslow (0.1Hz) sinusoidal waveform (50%), with the maximum current strength of 2.0 mA per electrode and the maximum total current injected being 4.0mA. Adherence of the intervention (i.e., duration of stimulation completed) will be recorded by the treating researcher.

The HD-tIGN-TNN will be delivered using a 32-channel Starstim transcranial electrical stimulator to alter the functional connectivity strength between the three cortical networks [namely the salience network (SN), the default mode network (DMN) and the somatomotor network (SMN)] in the infraslow frequency spectrum (0.1 Hz). A total of 16 circular Ag/AgCl electrodes [twelve stimulation electrodes (C5, C6, CPZ, F5, FC1, FC2, FT7, FT8, FPz, O2, T8, and TP7) and four electrodes with zero current (PO3, POZ, PO4, and O1)] will be placed on a neoprene head cap following the International 10-10 EEG system. The optimal montages has been created using the Stimweaver optimization software by the Neuroelectrics company, to specifically decrease/disrupt the functional connectivity i.e., communication hubs within the SN (i.e., rostral Anterior Cingulate Cortex, Insula) and CEN (i.e., Temporal Occipital Junction, Frontal Up, Frontal Down) are to be inhibited, and DMN hubs (i.e., Posterior Cingulate Cortex, Ventromedial Prefrontal Cortex, Temporoparietal Junction, Hippocampus) are to be excited.

This sub-study is conducted as part of the larger parent-trial (ACTRN12625000862448). It focuses specifically on the first treatment session of the parent-trial to investigate possible immediate outcomes from a single stimulation session. All participants enrolled in the parent-trial will partake in this sub-study, as outlined in the participant information sheet and consent form.
Intervention code [1] 332010 0
Treatment: Devices
Description of the comparator or control
For the sham condition, the set up will be identical to the HD-tIGN-TNN stimulation but no current will be applied (i.e., the Starstim device will remain off) for the length of the 30-minute session.
Control group
Placebo

Outcomes
Primary outcome [1] 342814 0
Resting state Electroencephalography as a measure of functional connectivity and will be calculated between the Central Executive Network and Salience Network
Timepoint [1] 342814 0
Directly pre-treatment and immediately post-treatment
Primary outcome [2] 342889 0
Change in Anxiety Symptom Severity
Timepoint [2] 342889 0
Directly pre-treatment and the following day post-treatment
Primary outcome [3] 342921 0
Resting state Electroencephalography as a measure of functional connectivity and will be calculated between the Central Executive Network and Default Mode Network
Timepoint [3] 342921 0
Directly pre-treatment and immediately post-treatment
Secondary outcome [1] 452705 0
(primary outcome) Resting state Electroencephalography as a measure of functional connectivity and will be calculated between the Salience Network and Default Mode Network
Timepoint [1] 452705 0
Directly pre-treatment and immediately post-treatment
Secondary outcome [2] 452706 0
Pupillometry, used to measure size of the pupils
Timepoint [2] 452706 0
Directly pre-treatment and immediately post-treatment
Secondary outcome [3] 452707 0
Resting state Electroencephalography as a measure of functional connectivity and will be calculated between the lateralized Central Executive, Salience, and Default Mode Networks
Timepoint [3] 452707 0
Directly pre-treatment and immediately post-treatment
Secondary outcome [4] 454232 0
Pupillometry, used to measure reactivity of the pupils
Timepoint [4] 454232 0
Directly pre-treatment and immediately post-treatment

Eligibility
Key inclusion criteria
Participants in this sub-study must be enrolled in the parent-study ACTRN12625000862448, for which the inclusion criteria are as follows (no further inclusion criteria are required for this sub-study):

Participants with a diagnosis of anxiety and/or depressive disorders (i.e., generalized anxiety disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, phobias, separation anxiety disorder, major depressive disorder, persistent depressive disorder) will be eligible to enroll in this study. Participants will need to be capable of understanding the study information and able to sign the informed consent form and:
• Aged between 18 to 45 years on the day of the consent.
• Have a total score of greater than or equal to 11 on the HADS, consistent with moderate or greater anxiety/depression severity.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
Participants in this sub-study must be enrolled in the parent-study ACTRN12625000862448, for which the exclusion criteria are as follows (there are no further exclusion criteria for this sub-study):

Participants who meet any of the following conditions will be excluded:
• History of neurological disorders.
• History of epilepsy or seizures.
• History of substance abuse (i.e., consuming more than 3 drinks on any day or more than 7 drinks per week for women, and more than 4 drinks on any day or more than 14 drinks per week for men).
• Previous treatment with neuromodulation (e.g. Transcranial magnetic or electrical stimulation, electroconvulsive therapy, Neurofeedback, etc.).
• Personality disorder, including borderline personality disorder.
• Cognitive impairments (e.g., dementia, Alzheimer’s disease, etc.): A total score of 24 or below on Mini-Mental State Examination.
• History of uncontrolled/untreated hypertension.
• Presence of any pacemaker or defibrillator.
• Presence of any electronic implants or metal implant in the body (particularly head and neck) that could impact the quality of physiological measurements.
• Recent (past six-months) or current pregnancy.
• Participants with current active suicidal ideation, assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS)

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)
The randomization schedule will be concealed in numbered, sealed, opaque envelopes. The envelopes will then be given directly to the treating researcher after the baseline session and before the first intervention session such that participants and the outcome assessor(s) remain blinded to the allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation sequence will be prepared by a research administrator not involved in assessment or intervention procedures using simple randomisation using a randomisation table created by computer software (i.e. computerised sequence
generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
As per the parent-study, sample size was not calculated for this study as it is a proof-of-concept trial. A modest sample of 30 participants (15 participants per group) will be recruited over a period of one year.
Primary and secondary outcome variables will be analyzed using R (R Core Team, Vienna, Austria, 2021; https://www.R-project.org/), RStudio (RStudio team, Boston, Massachusetts, United States of America (USA), 2020; http://www.rstudio.com/), and GraphPad Prism (GraphPad Software, Boston, Massachusetts, USA, www.graphpad.com). Note, the latest versions of these software programs at the time of analysis will be used, these will be documented in the clinical study report.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/02/2026
Actual
Date of last participant enrolment
Anticipated
31/08/2026
Actual
Date of last data collection
Anticipated
20/11/2026
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 27362 0
New Zealand
State/province [1] 27362 0
Otago

Funding & Sponsors
Funding source category [1] 319991 0
Charities/Societies/Foundations
Name [1] 319991 0
Whau Mental Health Foundation
Country [1] 319991 0
New Zealand
Primary sponsor type
University
Name
University of Otago Research and Enterprise Office
Address
Country
New Zealand
Secondary sponsor category [1] 322522 0
None
Name [1] 322522 0
Address [1] 322522 0
Country [1] 322522 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318529 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 318529 0
Ethics committee country [1] 318529 0
New Zealand
Date submitted for ethics approval [1] 318529 0
19/06/2025
Approval date [1] 318529 0
04/09/2025
Ethics approval number [1] 318529 0
2025 FULL 23366 

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 144482 0
Prof Dirk De Ridder
Address 144482 0
Department of Surgical Sciences Dunedin School of Medicine PO Box 56 Dunedin 9054
Country 144482 0
New Zealand
Phone 144482 0
+64275601144
Fax 144482 0
Email 144482 0
[email protected]
Contact person for public queries
Name 144483 0
Cindy van Sleeuwen
Address 144483 0
Department of Surgical Sciences Dunedin School of Medicine PO Box 56 Dunedin 9054 New Zealand
Country 144483 0
New Zealand
Phone 144483 0
+64 03 470 9337
Fax 144483 0
Email 144483 0
[email protected]
Contact person for scientific queries
Name 144484 0
Divya Adhia
Address 144484 0
Department of Surgical Sciences Dunedin School of Medicine PO Box 56 Dunedin 9054 New Zealand
Country 144484 0
New Zealand
Phone 144484 0
+64 03 470 9337
Fax 144484 0
Email 144484 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires a scientifically sound proposal or protocol
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
At the end of the study
To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
No


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.