Intermittent Theta Burst Transcranial Magnetic Stimulation of the Right Parietal Lobe in Anorexia Nervosa

Official title

Transcranial Magnetic Stimulation in Anorexia Nervosa: A Double-Blind Randomized Study on the Efficacy of Intermittent Theta Burst Stimulation of the Right Parietal Lobe

Overview

Anorexia Nervosa is a psychiatric disorder characterized by high rates of chronicity, significant societal costs, and one of the highest mortality rates among psychiatric illnesses. Despite therapeutic advances, treatment outcomes remain poor, with high relapse rates and full recovery achieved in only 50% of cases. Recent cognitive, behavioral, and neuroimaging studies suggest that Anorexia Nervosa may involve dysfunction in a posterior parietal network responsible for multisensory integration. This network plays a pivotal role in bodily self-representation and the modulation of environment-body interactions, and may therefore be directly implicated in two core symptoms of the disorder: distorted body image representation and dietary restriction. Given these insights, Transcranial Magnetic Stimulation (TMS) - an established neuromodulation technique with proven efficacy in various psychiatric disorders - emerges as a promising investigational intervention. The aim of this study is to evaluate the feasibility and therapeutic efficacy of a protocol of intermittent Theta Burst Stimulation (iTBS) targeting the right posterior parietal lobe in patients with Anorexia Nervosa. The active iTBS protocol will be compared to a sham (placebo) stimulation as a control condition.

Detailed description

Patients with anorexia nervosa will be recruited from the Eating Disorder Unit of Padova Hospital. Inclusion criteria will be: (1) current diagnosis of anorexia nervosa according to DSM-5 criteria; (2) 18 years or older; (3) failure of an outpatient treatment cycle lasting at least 3 months. Exclusion criteria will be: (1) Presence of significant neurological comorbidities or severe/unstable systemic diseases, (2) Diastolic blood pressure \<60 mmHg or heart rate \<60 bpm, (3) diagnosis of psychosis or substance abuse disorders, (4) history of hypomanic/manic episodes (5) Current suicidal ideation, (6) known contraindications to TMS (epilepsy, head trauma with loss of consciousness, severe/frequent headaches, cochlear implants, pacemakers, pregnancy, metallic implants, implanted neurostimulators)

Each patient will be randomly assigned to one of two conditions: active iTBS or sham stimulation

iTBS protocol: Patients in this condition will undergo 20 sessions of iTBS, one per day for 20 consecutive working days (4 weeks). Each visit will last approximately 20 minutes, including preparation, 3 minutes of stimulation, and debriefing. The coil position will be identified using a neuronavigation system based on each participant's MRI. Intermittent theta burst stimulation will involve the delivery of triplets of pulses at 50 Hz, repeated at 5 Hz, at 100% of the individual motor threshold.

Sham Stimulation: Patients in this condition will undergo the same protocol (20 sessions of TMS), with the only difference being the use of a sham coil, which produces the same sound as the real coil without generating a magnetic field

Patients in both conditions will complete a baseline assessment (Day 0), an end-of-treatment assessment (Week 4), and a follow-up assessment (4 months after the end of treatment).

All the assessments will include:

Clinical interview with a psychiatrist who is blind to the stimulation condition. During the interview, the clinician will also record the patients' weight and height to calculate Body Mass Index (BMI).

Depression Anxiety Stress Scales - 21 items (DASS-21): a validated 21-item scale for assessing depression, anxiety, and stress.

Eating Disorders Inventory (EDI-I): a validated 64-item scale for assessing eating disorder psychopathology.

Body Attitude Questionnaire: a validated questionnaire on body dissatisfaction and body perception.

Wisconsin Card Sorting Task (WCST): assessment of set-shifting abilities.

Rey-Osterrieth Complex Figure Test: assessment of central coherence.

Interventions

• Device Active iTBS
  Patients in this condition will undergo 20 sessions of iTBS, one per day for 20 consecutive working days (4 weeks). Each visit will last approximately 20 minutes, including preparation, 3 minutes of stimulation, and debriefing. The coil position will be identified using a neuronavigation system based on each participant's MRI. Intermittent theta burst stimulation will involve the delivery of triplets of pulses at 50 Hz, repeated at 5 Hz, at 100% of the individual motor threshold.
• Device Sham stimulation
  Patients in this condition will undergo 20 sessions of sham stimulation, one per day for 20 consecutive working days (4 weeks). Each visit will last approximately 20 minutes, including preparation, 3 minutes of stimulation, and debriefing. The coil position will be identified using a neuronavigation system based on each participant's MRI. Sham stimulation will be identical to active stimulation, with the only difference being the use of a sham coil, which produces the same sound as the real coil

Primary outcome measures

• Change from baseline in Body Mass Index (BMI) [Time frame: Day 0 (baseline), Week 4 (end of treatment), Week 20 (4-month follow-up)]

Secondary outcome measures (5)

• Change from baseline in depression, anxiety and stress [Time frame: Day 0 (baseline), Week 4 (end of treatment), Week 20 (4-month follow-up)]
• Change from baseline in eating disorder psychopathology [Time frame: Day 0 (baseline), Week 4 (end of treatment), Week 20 (4-month follow-up)]
• Change from baseline in body dissatisfaction and perception [Time frame: Day 0 (baseline), Week 4 (end of treatment), Week 20 (4-month follow-up)]
• Change from baseline in cognitive flexibility [Time frame: Day 0 (baseline), Week 4 (end of treatment), Week 20 (4-month follow-up)]
• Change from baseline in central coherence [Time frame: Day 0 (baseline), Week 4 (end of treatment), Week 20 (4-month follow-up)]

Eligibility criteria

Inclusion criteria

• Inclusion criteria will be: (1) current diagnosis of anorexia nervosa according to DSM-5 criteria; (2) 18 years or older; (3) failure of an outpatient treatment cycle lasting at least 3 months

Exclusion criteria

• Exclusion criteria will be: (1) Presence of significant neurological comorbidities or severe/unstable systemic diseases, (2) Diastolic blood pressure <60 mmHg or heart rate <60 bpm, (3) diagnosis of psychosis or substance abuse disorders, (4) history of hypomanic/manic episodes (5) Current suicidal ideation, (6) known contraindications to TMS (epilepsy, head trauma with loss of consciousness, severe/frequent headaches, cochlear implants, pacemakers, pregnancy, metallic implants, implanted neurostimulators)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Psychiatric Unit — Padova

Publications

• Meregalli V, Gentili S, Menardi A, Vallesi A, Olivo D, Manara R, Serino A, Risso G, Sambataro F, Favaro A, Collantoni E. Individualized targeting of the posterior parietal cortex with intermittent theta burst stimulation in anorexia nervosa: a randomized, double-blind, sham-controlled protocol. Front Neurosci. 2026 Jan 21;19:1733280. doi: 10.3389/fnins.2025.1733280. eCollection 2025. PMID 41648851

Identifiers

NCT: NCT07106645 · 6168/EST/25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗