Trial of Enhanced Neurostimulation for Anorexia (TRENA)

September 5, 2025 updated by: The George Institute

Randomised Controlled Trial of Neurostimulation for Symptoms of Anorexia Nervosa

Preliminary open-label studies have suggested that non-invasive brain stimulation methods of both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have clinical benefits for improving psychological and eating disorder related symptoms, which can persist at long-term follow ups after acute treatment (i.e., at 6 and 12 months).

Here the investigators propose to conduct the first double-blinded, randomised sham-controlled study to directly compare the therapeutic effectiveness and acceptability of both treatment modalities.

Participants will be recruited and treated at one inpatient setting (Northside Clinic, St Leonards, Sydney). This facility is one of the largest specialist eating disorder settings in Australia with approximately 130 new admissions every year (2019 data). All participants who give consent and who fulfill the eligibility criteria will be randomised to receive active tDCS, sham (placebo) tDCS, active rTMS or sham rTMS over 8 weeks. Trial participants, their treating psychiatrist, ward staff, and a study staff member (who will conduct blinded assessments of mood secondary outcome measures) will be blinded after assignment to intervention until the database is locked and the primary analysis completed. All participants will complete assessments of eating disorder symptoms, mood, psychological symptoms, neurocognition and functioning at baseline, end of week 4, 8 and 20.

Expected outcomes include data on the relative effectiveness and acceptability for both treatment modalities in the inpatient and at-home setting (i.e., for at-home tDCS). The investigators expect that both active treatment arms will produce clinical benefits and have high acceptability, and that clinical benefits will be maintained with long-term at-home tDCS continuation treatment. These outcomes have potential to assist in reducing hospital stay and emergency re-admissions and improving day to day functioning in participants. Health economic data for both treatment modalities will additionally have utility from a service perspective, given the disparity in resource requirements between the two treatments (TMS, tDCS) in terms of costs for patients and access to treatment for people living in remote and rural areas (i.e., for at-home tDCS).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2031
        • Recruiting
        • Northside Clinic
        • Principal Investigator:
          • Sloane Madden, Assoc. Prof.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged ≥16 years,
  • A current Diagnostic and Statistical Manual of Mental Disorders (5th edition DSM-5) diagnosis of anorexia nervosa
  • Willing and able to participate and comply with study requirements
  • Worked or studied in a context requiring some proficiency in spoken English (to ensure validity of neuropsychological testing)
  • Under ongoing care by his/her own treating psychiatrist (to ensure patient safety during the study)

Exclusion Criteria:

  • Inability to provide informed consent
  • Contraindications to tDCS/rTMS
  • Failed to respond to an adequate course or rTMS (4 weeks) within the current illness course
  • Had ECT in the last 3 months
  • MoCA score of <26
  • Significant risk of significant self harm or suicide as assessed by study psychiatrist(s)
  • Currently enrolled in another interventional clinical trial or using an investigational device/product

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active transcranial Direct Current Stimulation (tDCS)
It will be given continuously for 30 minutes at 2 mA, twice daily (separated by >=2 hours) over the first 4 weeks, and daily over the second 4 weeks of the 8 week acute treatment period (84 sessions total).
Device: tDCS mini-CT Stimulator (Soterix, USA: ARTG: 284637)
tDCS will be self-administered using the 1x1 tDCS mini-CT Stimulator (Soterix, USA: ARTG: 284637) with two saline-soaked sponge electrodes held in place on the scalp using the Soterix Ole-2 headband. The device is intended to treat different neurological and psychiatric disorders. tDCS involves the passing of weak electrical current through the brain via electrodes placed upon the scalp. The current modulates the resting membrane potential of stimulated neurons which causes changes in neuronal excitability. The anode will be placed over the left F3 (10-20 System) and the cathode over F4 (electrode sizes 5 x 5cm, 25cm2). This montage was chosen to target the left DLPFC, consistent with prior pilot studies of tDCS in AN.
Sham Comparator: Sham transcranial Direct Current Stimulation (tDCS)
It will involve an initial ramping up to 0.5 mA and then a ramp down to 0 mA for the remainder of each treatment. The same number of sessions as active tDCS will be administered.
Device: tDCS mini-CT Stimulator (Soterix, USA: ARTG: 284637)
tDCS will be self-administered using the 1x1 tDCS mini-CT Stimulator (Soterix, USA: ARTG: 284637) with two saline-soaked sponge electrodes held in place on the scalp using the Soterix Ole-2 headband. The device is intended to treat different neurological and psychiatric disorders. tDCS involves the passing of weak electrical current through the brain via electrodes placed upon the scalp. The current modulates the resting membrane potential of stimulated neurons which causes changes in neuronal excitability. The anode will be placed over the left F3 (10-20 System) and the cathode over F4 (electrode sizes 5 x 5cm, 25cm2). This montage was chosen to target the left DLPFC, consistent with prior pilot studies of tDCS in AN.
Active Comparator: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Active rTMS twice per day (separated by ≥ 2 hours) over the first 4 weeks. Two sessions per day (separated by ≥ 2 hours), given on 2 days each week for the following 4 weeks. The total number of rTMS sessions over the 8 week acute treatment period will be 56.
Device: MagPro TMS device (ARTG: 204659)
rTMS will be administered using a MagPro TMS device (ARTG: 204659) which is approved for its intended use in this trial. rTMS involves the application of transient magnetic pulses which induce small currents in the underlying cortex via the principal of electromagnetic induction. rTMS will be administered using a patterned frequency stimulus called intermittent theta-burst stimulation (iTBS).This form of rTMS was chosen because a recent large multicentre trial showed 3 minutes of iTBS attained the same therapeutic effect as 30 minutes of standard rTMS, leading to FDA approval for depression. Each treatment session will comprise an extended iTBS session, i.e., 6.6 mins, delivered at 100% resting motor threshold (RMT). It will be targeted to the left DLPFC (F3 using the 10-20 International EEG system), consistent with the prior RCT of rTMS for AN.
Sham Comparator: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Sham rTMS twice per day (separated by ≥ 2 hours) over the first 4 weeks. Two sessions per day (separated by ≥ 2 hours), given on 2 days each week for the following 4 weeks. The same number of sessions as active rTMS will be administered.
Device: MagPro TMS device (ARTG: 204659)
rTMS will be administered using a MagPro TMS device (ARTG: 204659) which is approved for its intended use in this trial. rTMS involves the application of transient magnetic pulses which induce small currents in the underlying cortex via the principal of electromagnetic induction. rTMS will be administered using a patterned frequency stimulus called intermittent theta-burst stimulation (iTBS).This form of rTMS was chosen because a recent large multicentre trial showed 3 minutes of iTBS attained the same therapeutic effect as 30 minutes of standard rTMS, leading to FDA approval for depression. Each treatment session will comprise an extended iTBS session, i.e., 6.6 mins, delivered at 100% resting motor threshold (RMT). It will be targeted to the left DLPFC (F3 using the 10-20 International EEG system), consistent with the prior RCT of rTMS for AN.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness - Eating Disorder Examination Questionnaire (EDE Q)
Time Frame: Change from baseline at 8 weeks
Self-report instrument that measures eating disorder behaviors and attitudes. Eating Disorder Examination Questionnaire; 28-items; rating scale 0 - 6; Higher scores on the global scale and subscales indicate more problematic eating behaviours and attitudes.
Change from baseline at 8 weeks
Acceptability
Time Frame: 8 weeks
Number of completed sessions for active tDCS and active rTMS in the acute 8 week RCT period.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weight
Time Frame: Change from baseline at 4 weeks
Change in Body Mass Index. Weight status in AN is considered a key determinant of remission from illness.
Change from baseline at 4 weeks
Weight
Time Frame: Change from baseline at 8 weeks
Change in Body Mass Index. Weight status in AN is considered a key determinant of remission from illness.
Change from baseline at 8 weeks
Weight
Time Frame: Change from baseline at 20 weeks
Change in Body Mass Index. Weight status in AN is considered a key determinant of remission from illness.
Change from baseline at 20 weeks
Mood - Montgomery Asberg Depression Rating Score (MADRS)
Time Frame: Change from baseline at 4 weeks
Depressive symptomology is a common psychiatric comorbidity of AN and both tDCS and rTMS significantly improve mood symptoms. 10-items; rating scale 0- 6; Higher score indicates more severe depression.
Change from baseline at 4 weeks
Mood - Montgomery Asberg Depression Rating Score (MADRS)
Time Frame: Change from baseline at 8 weeks
Depressive symptomology is a common psychiatric comorbidity of AN and both tDCS and rTMS significantly improve mood symptoms. 10-items; rating scale 0- 6; Higher score indicates more severe depression.
Change from baseline at 8 weeks
Mood - Montgomery Asberg Depression Rating Score (MADRS)
Time Frame: Change from baseline at 20 weeks
Depressive symptomology is a common psychiatric comorbidity of AN and both tDCS and rTMS significantly improve mood symptoms. 10-items; rating scale 0- 6; Higher score indicates more severe depression.
Change from baseline at 20 weeks
Neurocognition - Trail Making Test parts A and B (TMT: attention and cognitive flexibility)
Time Frame: Change from baseline at 8 weeks
Deficits in set shifting has been found to be common in people with AN.
Change from baseline at 8 weeks
Neurocognition - Trail Making Test parts A and B (TMT: attention and cognitive flexibility)
Time Frame: Change from baseline at 20 weeks
Deficits in set shifting has been found to be common in people with AN.
Change from baseline at 20 weeks
Neurocognition - Embedded Figures Test (EFT: field dependence vs independence).
Time Frame: Change from baseline at 8 weeks
This task assesses central coherence, or the degree of focus on details in processing information. Poor central coherence is a potential etiologic or maintaining factor for people with eating disorders.
Change from baseline at 8 weeks
Neurocognition - Embedded Figures Test (EFT: field dependence vs independence).
Time Frame: Change from baseline at 20 weeks
This task assesses central coherence, or the degree of focus on details in processing information. Poor central coherence is a potential etiologic or maintaining factor for people with eating disorders.
Change from baseline at 20 weeks
Neurocognition - STROOP Colour Word Test (response inhibition).
Time Frame: Change from baseline at 8 weeks
The STROOP task assesses inhibitory control, which has been shown to be reduced in people with eating disorders.
Change from baseline at 8 weeks
Neurocognition - STROOP Colour Word Test (response inhibition).
Time Frame: Change from baseline at 20 weeks
The STROOP task assesses inhibitory control, which has been shown to be reduced in people with eating disorders.
Change from baseline at 20 weeks
Neurocognition - Wisconsin Card Sorting Test (WSCT: perseveration).
Time Frame: Change from baseline at 8 weeks
This task has been found to be sensitive to set shifting deficits in people with AN.
Change from baseline at 8 weeks
Neurocognition - Wisconsin Card Sorting Test (WSCT: perseveration).
Time Frame: Change from baseline at 20 weeks
This task has been found to be sensitive to set shifting deficits in people with AN.
Change from baseline at 20 weeks
Psychological Symptoms - Depression Anxiety and Stress Scale (DASS-21)
Time Frame: Change from baseline at 8 weeks
Self reported questionnaire designed to measure the severity of a range of symptoms common to both Depression and Anxiety. 21-items; rating scale 0- 3; Higher scores on subscales indicate more severe depression, anxiety and stress.
Change from baseline at 8 weeks
Psychological Symptoms - Depression Anxiety and Stress Scale (DASS-21)
Time Frame: Change from baseline at 20 weeks
Self reported questionnaire designed to measure the severity of a range of symptoms common to both Depression and Anxiety. 21-items; rating scale 0- 3; Higher scores on subscales indicate more severe depression, anxiety and stress.
Change from baseline at 20 weeks
Functioning - The Assessment of Quality of Life Instrument (AQoL-4D)
Time Frame: Change from baseline at 8 weeks
Measures quality of life for independent living, mental health, relationships, and senses. It as chosen as measures can be used for economic evaluation based on Quality Adjusted Life Years (QALYs). 12-items; scale 1-4; Higher score indicates lower health-related quality of life.
Change from baseline at 8 weeks
Functioning - The Assessment of Quality of Life Instrument (AQoL-4D)
Time Frame: Change from baseline at 20 weeks
Measures quality of life for independent living, mental health, relationships, and senses. It as chosen as measures can be used for economic evaluation based on Quality Adjusted Life Years (QALYs). 12-items; scale 1-4; Higher score indicates lower health-related quality of life.
Change from baseline at 20 weeks
Change in Circumplex Scales of Interpersonal Efficacy (CSIE-32)
Time Frame: Change from baseline at 8 weeks
Change in Circumplex Scales of Interpersonal Efficacy: 32-items; scale 0-10; Higher score indicate confidence that one can engage in variety of interpersonal behaviours.
Change from baseline at 8 weeks
Change in Circumplex Scales of Interpersonal Efficacy (CSIE-32)
Time Frame: Change from baseline at 20 weeks
Change in Circumplex Scales of Interpersonal Efficacy: 32-items; scale 0-10; Higher score indicate confidence that one can engage in variety of interpersonal behaviours.
Change from baseline at 20 weeks
Total cost of costs of rTMS and tDCS administration
Time Frame: Through study completion, an average of 20 weeks
Total cost of costs of rTMS and tDCS administration
Through study completion, an average of 20 weeks
Duration of inpatient hospital stay as recorded by clinical staff
Time Frame: Through study completion, an average of 20 weeks
Duration of inpatient hospital stay as recorded by clinical staff
Through study completion, an average of 20 weeks
Number of re-admissions as reported by clinical staff.
Time Frame: From date of randomization until the date of study completion, assessed up to 20 weeks.
Number of re-admissions as reported by clinical staff
From date of randomization until the date of study completion, assessed up to 20 weeks.
Number of psychology sessions
Time Frame: Through study completion, an average of 20 weeks
Number of psychology sessions
Through study completion, an average of 20 weeks
Cost of psychology sessions
Time Frame: Through study completion, an average of 20 weeks
Cost of psychology sessions in $ AUD
Through study completion, an average of 20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The George Institute

Collaborators

The University of New South Wales

Investigators

  • Principal Investigator: Sloane Madden, Assoc. Prof., University of Sydney, Ramsay Health Care

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2023

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

February 21, 2023

First Submitted That Met QC Criteria

March 15, 2023

First Posted (Actual)

March 28, 2023

Study Record Updates

Last Update Posted (Estimated)

September 12, 2025

Last Update Submitted That Met QC Criteria

September 5, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All de-identified data though with ethics approval and data transfer agreements required

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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