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Trial registered on ANZCTR


Registration number
ACTRN12623001146684
Ethics application status
Approved
Date submitted
5/09/2023
Date registered
6/11/2023
Date last updated
19/02/2024
Date data sharing statement initially provided
6/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Functional Connectivity-informed Individualised Transcranial Magnetic Stimulation Therapy for Anorexia Nervosa (FUNCTIAN)
Scientific title
Functional Connectivity-informed Individualised Transcranial Magnetic Stimulation Therapy for Anorexia Nervosa (FUNCTIAN) – An Open-Label Proof of Concept Study
Secondary ID [1] 310549 0
None
Universal Trial Number (UTN)
Trial acronym
FUNCTIAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anorexia Nervosa 331376 0
Condition category
Condition code
Mental Health 328124 328124 0 0
Eating disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
iTBS will be administered with a magnetic stimulator using a figure-of-8 coil or equivalent FDA-approved device. Calibration of stimulation intensity based on the resting motor threshold will be conducted by TMS-trained investigators/staff at the Monash Alfred Psychiatry Research Centre using standard approaches. Stimulation intensity will be at 90% of the participant’s resting motor threshold.

Treatment coil localisation will be based on the cortical coordinates derived using individual MRI scans. The corresponding scalp coordinates will then be determined using an optical neuronavigation system (e.g. the Localite TMS Navigator and Software, Localite GmbH, Bonn, Germany). These coordinates will be recorded, to ensure accurate and consistent coil placement for each subsequent treatment session.

In the first month, participants will receive 30 Intermittent theta burst stimulation (iTBS) treatment sessions in the first 3 weeks, termed the ‘Acute Phase.’ Two iTBS sessions will be applied per day, 5-days a week, to deliver 30 sessions over 3 weeks. In the maintenance Phase (Months 2-6), participants will receive 10 iTBS treatment sessions per month, where 2 sessions are delivered per day, scheduled on days of their preference/research team’s capacity. Each month, the 10 scheduled iTBS sessions will be completed within 10 calendar days. Each iTBS session is approximately 10 minutes in duration.
Intervention code [1] 326944 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335998 0
Body Mass Index (BMI) - Height measured by stadiometer and weight measured by digital scales
Timepoint [1] 335998 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Primary outcome [2] 335999 0
Eating Disorder Examination Questionnaire (EDE-Q)
Timepoint [2] 335999 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Primary outcome [3] 336000 0
Change in Eating Disorder Symptoms (CHEDS) Scale
Timepoint [3] 336000 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [1] 426441 0
Readiness to Change Score
Timepoint [1] 426441 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [2] 426442 0
Disordered Eating Attitude Scale (DEAS)
Timepoint [2] 426442 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [3] 426443 0
Eating Disorder Recovery Self-Efficacy Questionnaire (EDRSQ)
Timepoint [3] 426443 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [4] 426444 0
Depression, Anxiety and Stress Scale (DASS-21). This will be assessed as a composite outcome.
Timepoint [4] 426444 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [5] 426445 0
Obsessive-Compulsive Inventory (OCI)
Timepoint [5] 426445 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [6] 426446 0
The International Trauma Questionnaire (ITQ)
Timepoint [6] 426446 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.
Secondary outcome [7] 426447 0
World Health Organization Quality of Life (WHOQoL)
Timepoint [7] 426447 0
Baseline, end of Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 and Month 12 post-baseline.

Eligibility
Key inclusion criteria
1. Diagnosis of anorexia nervosa (restrictive or binge-eating/purging subtype), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), of greater than 3 years duration.
2. 18 years or older in age.
3. Baseline body mass index (BMI) between 15 and 18.
4. No initiation of therapies targeting AN within the 4 weeks prior to screening. This includes pharmacological and psychological therapies.
5. No increase or initiation of medications with appetite suppressing and/or weight loss effects within the 4 weeks prior to screening.
6. Demonstrated capacity to give informed consent.
7. Participants who are engaged with an existing clinical treatment team for their AN at the time of enrolment and over the course of trial participation. For this purpose, engagement is defined as maintaining clinical contact, on average, at least every 4 weeks.
8. Consent for the research team to communicate with the participant’s clinical treatment team in regard to a) Their progress through the trial and b) Communicate clinical deterioration and risks to allow facilitation of appropriate management, where clinically-indicated.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to provide informed consent.
2. Hospitalisation within the 8 weeks prior to screening for treatment of medical compromise or instability resulting from AN.
3. Physical parameters meeting Criteria* for Medical Ward Admission as per the Alfred Health Eating Disorder – Inpatient Access and Treatment Pathways Guideline, namely:
a. High refeeding risk;
b. Vital signs as follows:
i. Systolic BP < 80 mmHg;
ii. Postural BP drop > 20 mmHg systolic, > 10 mmHg diastolic;
iii. Heart rate < 40 or > 110;
iv. Temperature < 35.5°C.
c. Blood tests within the preceding 7 days showing:
i. Blood Glucose <3.0 mmol/L
ii. Serum sodium <130 mmol/L
iii. Serum magnesium < 0.6 mmol/L
iv. Serum potassium <3.0 mmol/L
v. Serum phosphate <0.7 mmol/L
vi. Glomerular filtration rate < 60ml/min (Cockroft-Gault)
vii. Albumin <27 g/L
viii. Liver Enzymes ALT > 3 x upper limit of normal
ix. Neutrophils <1.0x10^9/L
*Unless the condition was assessed to be pre-existing or otherwise doesn’t present a severity of illness that should exclude the participant on the basis of safety, at the discretion of the study medical doctor.
d. GCS <15
4. Other clinically significant cardiac, respiratory, renal or endocrine conditions, or evidence of medical instability, at the discretion of the investigator.
5. Concomitant neurological disorder or a history of a seizure disorder.
6. Any contraindication to undergo MRI.
7. Participants who are pregnant.
8. Current substance use meeting DSM-5 criteria for substance use disorder, excluding nicotine use disorder.
9. Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder or delusional disorder as assessed by the Structured Clinical Interview for DSM-5 (SCID-5) at the time of screening.
10. Diagnosis of any other mental disorder that is the participant’s primary diagnosis or main mental health syndrome of concern at the time of screening, which may significantly affect psychiatric status and assessed as likely to impact trial participation, in the clinical judgement of the investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 314751 0
Other
Name [1] 314751 0
Monash Alfred Psychiatry Research Centre
Country [1] 314751 0
Australia
Primary sponsor type
University
Name
Monash University
Address
External Relations, Development and Alumni
Locked Bag 7
MONASH UNIVERSITY VIC 3800
Country
Australia
Secondary sponsor category [1] 316734 0
None
Name [1] 316734 0
Address [1] 316734 0
Country [1] 316734 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313760 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313760 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 313760 0
Australia
Date submitted for ethics approval [1] 313760 0
06/09/2023
Approval date [1] 313760 0
08/12/2023
Ethics approval number [1] 313760 0

Summary
Brief summary
Anorexia nervosa (AN) is a serious psychiatric condition with high morbidity and mortality, for which existing treatment paradigms demonstrate suboptimal therapeutic efficacy and duration of treatment effect. Through the repeated application of focussed electromagnetic energy, Repetitive Transcranial Magnetic Stimulation (rTMS) can modulate cortical neural activity and connectivity downstream, along the brain circuits that the cortical target is connected to. rTMS has the added benefits of being non-invasive, has high degrees of patient acceptance and tolerability, as well as being relatively economical to apply. As an evidence-based treatment for depression, rTMS has received little research attention in AN. Clinical trials to date indicate therapeutic optimism, particularly in relation to subjective anorexia-related experiences and comorbid mood, anxiety, stress, and quality of life symptoms.

This study protocol proposes the conduct of a single-site, proof-of-concept, open-label trial to evaluate if this individualised rTMS targeting and stimulation approach is effective in improving the low body mass and psychological symptoms in anorexia nervosa from baseline to the end of week 4, and the durability of these effects at 6- and 12-month follow-up.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129274 0
Dr Leo Chen
Address 129274 0
Monash Alfred Psychiatry Research, Centre Level 4, 607 St Kilda Rd Melbourne VIC 3004
Country 129274 0
Australia
Phone 129274 0
+61 3 90766564
Fax 129274 0
Email 129274 0
leo.chen@monash.edu
Contact person for public queries
Name 129275 0
Ms Kaila Bianco
Address 129275 0
Monash Alfred Psychiatry Research, Centre Level 4, 607 St Kilda Rd Melbourne VIC 3004
Country 129275 0
Australia
Phone 129275 0
+61 3 9076 6564
Fax 129275 0
Email 129275 0
tms-trials@monash.edu
Contact person for scientific queries
Name 129276 0
Dr Leo Chen
Address 129276 0
Monash Alfred Psychiatry Research, Centre Level 4, 607 St Kilda Rd Melbourne VIC 3004
Country 129276 0
Australia
Phone 129276 0
+61 3 9076 6564
Fax 129276 0
Email 129276 0
leo.chen@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.