Circuit-Guided Neuromodulation for Anorexia Nervosa

ConditionAnorexia Nervosa

Trial statusNot yet recruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18-65

SponsorFundacao Champalimaud

About this trial

The goal of this clinical trial is to find out whether personalized, non-invasive brain stimulation can temporarily change communication within brain networks related to restrictive eating in adults with anorexia nervosa.

The main questions this study aims to answer are:

* Does personalized transcranial magnetic stimulation (TMS) change functional connectivity within a brain network related to restrictive eating compared with sham stimulation? * Do different types of TMS affect measures related to inhibitory control, body image, eating-disorder symptoms, mood, and anxiety, and are they safe and well tolerated?

Participants will:

* Attend four study visits, separated by at least one week. * Complete clinical and psychological assessments and undergo brain magnetic resonance imaging (MRI). * Receive three stimulation conditions in random order at separate visits: intermittent theta-burst stimulation (iTBS), continuous theta-burst stimulation (cTBS), and sham stimulation. * Complete brain MRI scans and research tasks so that the effects of the three stimulation conditions can be compared.

Researchers will compare the effects of iTBS and cTBS with sham stimulation on brain connectivity and other study measures.

This is an exploratory proof-of-concept study designed to test whether personalized brain stimulation can engage the targeted brain circuit. It is not designed to determine whether TMS is an effective treatment for anorexia nervosa, and direct clinical benefit to participants is not expected.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age between 18 and 65 years, inclusive.

Established diagnosis of anorexia nervosa according to DSM-5 criteria, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5) at Visit 1.

Capacity to provide written informed consent, as assessed by the investigator at Visit 1.

Fluency in European Portuguese sufficient to complete the study assessments.

Disqualifiers

Current manic or psychotic episode.

Major or minor neurocognitive disorder.

Neurodevelopmental disorder, including attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD).

Any medical or psychiatric condition requiring immediate hospitalization at the time of enrollment. Psychiatry day hospital care does not constitute an exclusion criterion.

Trial design

Design model

Crossover

Treatments tested in this trial

Intermittent theta-burst stimulation (iTBS)
Device
A single session of neuronavigated intermittent theta-burst stimulation (iTBS) is delivered using a MagVenture MagPro X100 with MagOption and the appropriate active coil (Cool-B65 or Cool-D-B80) selected according to the individualized target. Stimulation is delivered at 80% of the individual resting motor threshold (RMT) to a personalized prefrontal site defined using lesion network mapping and SimNIBS. Bursts are delivered at 5 Hz, with 3 pulses at 50 Hz per burst, in an intermittent pattern of 2 seconds ON and 8 seconds OFF, for a total of 600 pulses over approximately 190 seconds.
Continuous theta-burst stimulation (cTBS)
Device
A single session of neuronavigated continuous theta-burst stimulation (cTBS) is delivered using a MagVenture MagPro X100 with MagOption and the appropriate active coil (Cool-B65 or Cool-D-B80) selected according to the individualized target. Stimulation is delivered at 80% of the individual resting motor threshold (RMT) to a personalized prefrontal site defined using lesion network mapping and SimNIBS. Bursts are delivered at 5 Hz, with 3 pulses at 50 Hz per burst, continuously without interruption, for a total of 600 pulses over approximately 40 seconds.
Sham theta-burst stimulation
Device
A single session of sham theta-burst stimulation is delivered using the MagVenture MagPro X100 with MagOption and a shielded sham coil at the individualized prefrontal target. Coil positioning, neuronavigation display, and auditory and somatosensory characteristics are matched as closely as possible to the active conditions. The programmed sham protocol uses 5-Hz bursts with 3 pulses at 50 Hz per burst, an intermittent pattern of 5 seconds ON and 10 seconds OFF, 600 pulses, a session duration of 110 seconds, and an intensity setting of 80% of the individual RMT.

Treatment groups

30 Participants

are divided into 3 treatment groups

Group A: Intermittent Theta-Burst Stimulation (iTBS)Experimental treatment 1 intervention

Group B: Continuous Theta-Burst Stimulation (cTBS)Experimental treatment 1 intervention

Group C: Sham Theta-Burst StimulationSham comparator 1 intervention

Trial outcomes

Primary outcomes

Post-Stimulation Target-to-Network Resting-State fMRI Functional Connectivity

Resting-state fMRI functional connectivity between the individualized prefrontal stimulation target and the lesion-defined restrictive-eating network, quantified using the target-to-network connectivity index. The measure is assessed after each iTBS, cTBS, and sham session and compared within participants across the three stimulation conditions.

Time frame

Within approximately 30 minutes after each stimulation session at crossover Visits 2, 3, and 4 (Weeks 2, 4, and 6; visits separated by at least 1 week)

Secondary outcomes

GNAT Inhibitory-Control Performance (d-prime) After Stimulation

Inhibitory-control performance assessed using the Go/No-Go Association Task (GNAT) with food and non-food stimuli. The pre-specified outcome metric is d-prime, assessed following each stimulation condition and compared within participants across iTBS, cTBS, and sham.

Time frame

During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes after stimulation

Body Discrepancy Index After Stimulation

Body-image evaluation assessed using a 7-silhouette body-image task adapted for scanner administration. The primary metric is the body discrepancy index, based on the difference between perceived and ideal body silhouettes, and is compared within participants across iTBS, cTBS, and sham conditions.

Time frame

During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes after stimulation

Post-Stimulation Task-Based fMRI BOLD Signal in the Lesion-Defined Network

Blood-oxygen-level-dependent (BOLD) signal measured in pre-specified regions of interest within the lesion-defined restrictive-eating network during the GNAT and body-image task paradigms. BOLD responses are compared within participants across iTBS, cTBS, and sham conditions.

Time frame

During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes after stimulation

Eating Disorder Psychopathology Assessed With the EDE-Q

Eating-disorder psychopathology assessed using the Eating Disorder Examination Questionnaire (EDE-Q), version 6.0. The pre-specified metric is the EDE-Q total score. Higher scores indicate greater eating-disorder psychopathology. The EDE-Q is administered before stimulation at each crossover visit.

Time frame

Pre-stimulation at crossover Visits 2, 3, and 4 (approximately Weeks 2, 4, and 6; visits separated by at least 1 week)

Other outcomes

Incidence and Nature of Adverse Events and Device-Related Safety Events

Incidence and nature of adverse events (AEs), serious adverse events (SAEs), serious adverse device effects (SADEs), and device deficiencies. Pre-specified TMS-specific safety events include seizure, syncope, severe headache, and severe mood change. Events will be summarized descriptively by stimulation condition.

Time frame

From enrollment at Visit 1 through completion of Visit 4 (approximately 4-7 weeks per participant)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fundacao Champalimaud

Lead sponsor

Source ClinicalTrials.gov

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