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Trial registered on ANZCTR


Registration number
ACTRN12625000862448p
Ethics application status
Submitted, not yet approved
Date submitted
22/07/2025
Date registered
8/08/2025
Date last updated
8/08/2025
Date data sharing statement initially provided
8/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring the Effect of a Brain Stimulation Approach on Symptoms in Adults with Anxiety and Depression
Scientific title
A Triple Network Stimulation Approach for the Treatment of Internalizing Psychopathology in Adults: A Proof-of-Concept Study (TNS-IP Trial)
Secondary ID [1] 314949 0
None
Universal Trial Number (UTN)
Trial acronym
TNS-IP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety disorders 338266 0
Depressive disorders 338269 0
Condition category
Condition code
Mental Health 334566 334566 0 0
Anxiety
Mental Health 334567 334567 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High-definition transcranial Infraslow Grey Noise Triple Network Neuromodulation (HD-tIGN-TNN) stimulation intervention will be administered three times per week for three (delayed-start arm [following 3-weeks of sham]), or six weeks (early-start arm), by a researcher experienced in administering neuromodulation techniques (i.e, 9, or 18 sessions in total, respectively). The Starstim-20 TES device (Neuroelectrics, Spain) will be used to deliver stimulation while participants are comfortably seated. Stimulation electrodes will be placed following the 10/20 electroencephalography (EEG) system to target the triple brain network in its anti-correlated way and to dissociate the correlated activity of the triple brain networks. The optimal montage for the triple brain network stimulation is created using the Stimweaver optimization software by Neuroelectrics company. The placement of electrodes will be identical for both sham and HD-tIGN-TNN conditions.
For the HD-tIGN-TNN condition, the stimulation will be delivered at a current strength of maximum of 4mA for 30min, with 60s ramp up and ramp down at the beginning and end of each stimulation session, with continuous stimulation in between. The grey noise stimulation at a current strength of maximum of 1.5mA will be superimposed on the infraslow stimulation waveform of a current intensity of 1.515mA, such that the current strength of the waveform never exceeds the maximum of 4mA. The intervention dosage is chosen based on previous studies by our group and following the safety guidelines.
Intervention sessions are held at the Dunedin Public Hospital, New Zealand.
A trained researcher will measure intervention adherence for all participants. Specifically, this will be recorded and monitored on a sheet where intervention attendance is logged per session.
Intervention code [1] 331551 0
Treatment: Devices
Comparator / control treatment
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] 342244 0
Change in Anxiety symptom severity
Timepoint [1] 342244 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Primary outcome [2] 342253 0
Change in Depression symptom severity
Timepoint [2] 342253 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Primary outcome [3] 342254 0
Safety of the Intervention
Timepoint [3] 342254 0
End of the first, 9th, 10th, and 18th intervention session
Secondary outcome [1] 450069 0
Change in Intolerance of Uncertainty
Timepoint [1] 450069 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [2] 450070 0
Participants impression of change (self report)
Timepoint [2] 450070 0
Immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [3] 450071 0
Change in Depression, Anxiety, and Stress scores as a composite
Timepoint [3] 450071 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [4] 450072 0
Changes in Wellbeing
Timepoint [4] 450072 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [5] 450073 0
Changes in Fatigue
Timepoint [5] 450073 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [6] 450074 0
Changes in Sleep Quality
Timepoint [6] 450074 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [7] 450075 0
Changes in overall Suffering
Timepoint [7] 450075 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [8] 450138 0
Brain functional connectivity
Timepoint [8] 450138 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [9] 450408 0
Change in depression score
Timepoint [9] 450408 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [10] 450409 0
Change in anxiety score
Timepoint [10] 450409 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups
Secondary outcome [11] 450410 0
Change in stress score
Timepoint [11] 450410 0
Baseline, mid-intervention, immediately post-intervention and two-week and one-month post-intervention follow-ups

Eligibility
Key inclusion criteria
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
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
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
Safety/efficacy
Statistical methods / analysis
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/), IBM Statistical Package for Social Sciences (SPSS) for Windows (Version 28, IBM Corp, Armonk, New York, USA) and/or 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
18/08/2025
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] 27247 0
New Zealand
State/province [1] 27247 0
Otago

Funding & Sponsors
Funding source category [1] 319507 0
Charities/Societies/Foundations
Name [1] 319507 0
Whau Mental Health Foundation
Country [1] 319507 0
New Zealand
Primary sponsor type
University
Name
University of Otago Research and Enterprise Office
Address
Country
New Zealand
Secondary sponsor category [1] 322005 0
None
Name [1] 322005 0
Address [1] 322005 0
Country [1] 322005 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 318083 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 318083 0
Ethics committee country [1] 318083 0
New Zealand
Date submitted for ethics approval [1] 318083 0
19/06/2025
Approval date [1] 318083 0
Ethics approval number [1] 318083 0
2025 FULL 23366 

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

Contacts
Principal investigator
Name 143054 0
Prof Dirk De Ridder
Address 143054 0
Department of Surgical Sciences Dunedin School of Medicine PO Box 56 Dunedin 9054
Country 143054 0
New Zealand
Phone 143054 0
+64275601144
Fax 143054 0
Email 143054 0
[email protected]
Contact person for public queries
Name 143055 0
Cindy van Sleeuwen
Address 143055 0
Department of Surgical Sciences Dunedin School of Medicine PO Box 56 Dunedin 9054 New Zealand
Country 143055 0
New Zealand
Phone 143055 0
+64 03 470 9337
Fax 143055 0
Email 143055 0
[email protected]
Contact person for scientific queries
Name 143056 0
Divya Adhia
Address 143056 0
Department of Surgical Sciences Dunedin School of Medicine PO Box 56 Dunedin 9054 New Zealand
Country 143056 0
New Zealand
Phone 143056 0
+64 03 470 9337
Fax 143056 0
Email 143056 0
[email protected]

Data sharing statement
Will the study consider sharing 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.