None listed
Conditions
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.
Interventions
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 s
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.
Sponsors
Monash University
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed