Circuit-Guided Neuromodulation for Anorexia Nervosa (RestrEAT)

October 1, 2026 updated by: Fundacao Champalimaud

Re-tuning Restrictive Eating Circuits: From Lesion Network Mapping to Personalized Neuromodulation Targets

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

RestrEAT is a mechanistic, proof-of-concept investigation designed to evaluate a personalized, circuit-guided targeting strategy for prefrontal theta-burst stimulation (TBS) in anorexia nervosa.

The targeting framework is based on a lesion-defined restrictive-eating network derived from brain lesions associated with restrictive eating and anorexia-nervosa-like psychopathology. For each participant, individualized electric-field modelling using SimNIBS is combined with functional connectivity derived from the participant's baseline fMRI data. Candidate TMS-accessible prefrontal sites are evaluated, and the stimulation site is selected according to the similarity between its individual functional connectivity profile and the lesion-defined network. The individualized target is subsequently implemented using neuronavigation.

The study is intended to generate mechanistic target-engagement data rather than establish the therapeutic efficacy of TMS for anorexia nervosa. The within-subject crossover design was selected because the effects of a single TBS session are expected to be acute and transient, allowing comparison of stimulation conditions within the same participant while reducing variability related to inter-individual differences in functional connectivity and cognitive performance.

The results are intended to evaluate the feasibility and biological validity of the personalized targeting approach, characterize effect-size estimates, and inform the design of a subsequent adequately powered therapeutic clinical trial if supported by the findings.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Portugal
    • Lisbon District
      • Lisbon, Lisbon District, Portugal, 1400-038
        • Champalimaud Foundation
        • Principal Investigator:
          • Albino J. Oliveira-Maia, MD, MPH, PhD
        • Principal Investigator:
          • Gonçalo Cotovio, MD, PhD
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • History of a structural lesion of the central nervous system.
  • Presence of electrical or metallic implants incompatible with TMS or MRI, including cochlear implants, deep brain stimulators, vagus nerve stimulators, cardiac pacemakers, implantable cardioverter-defibrillators, intracardiac lines, or aneurysm clips or coils, in accordance with the manufacturer's contraindications.
  • Personal history of epilepsy or unexplained loss of consciousness.
  • Any contraindication to TMS or MRI.
  • Pregnancy or breastfeeding at the time of enrollment.
  • For participants of childbearing potential, lack of use of an effective method of contraception throughout the study period.

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intermittent Theta-Burst Stimulation (iTBS)

Participants receive one session of personalized prefrontal intermittent theta-burst stimulation (iTBS) during one of the three randomized crossover stimulation visits. Each participant receives this condition once, with a washout interval of at least one week between stimulation visits.
Device: Intermittent theta-burst stimulation (iTBS)

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.
Experimental: Continuous Theta-Burst Stimulation (cTBS)

Participants receive one session of personalized prefrontal continuous theta-burst stimulation (cTBS) during one of the three randomized crossover stimulation visits. Each participant receives this condition once, with a washout interval of at least one week between stimulation visits.
Device: Continuous theta-burst stimulation (cTBS)

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 Comparator: Sham Theta-Burst Stimulation

Participants receive one session of sham theta-burst stimulation during one of the three randomized crossover stimulation visits. Each participant receives this condition once, with a washout interval of at least one week between stimulation visits.
Device: Sham theta-burst stimulation

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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Post-Stimulation Target-to-Network Resting-State fMRI Functional Connectivity
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)

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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
GNAT Inhibitory-Control Performance (d-prime) After Stimulation
Time Frame: During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes 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.
During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes after stimulation
Body Discrepancy Index After Stimulation
Time Frame: During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes 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.
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
Time Frame: During post-stimulation task-based fMRI at crossover Visits 2, 3, and 4, within approximately 30 minutes after stimulation

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

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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence and Nature of Adverse Events and Device-Related Safety Events
Time Frame: From enrollment at Visit 1 through completion of Visit 4 (approximately 4-7 weeks per participant)

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

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundacao Champalimaud

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gonçalo Cotovio, MD, PhD, Champalimaud Foundation
  • Study Director: Albino J. Oliveira-Maia, MD, MPH, PhD, Champalimaud Foundation

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 1, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 6, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RestrEAT
  • 723209 (Registry Identifier: Registo Nacional de Estudos Clínicos (RNEC), Portugal)
  • 2626CI_RESTREAT (Other Identifier: INFARMED - Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is currently no plan to make individual participant data (IPD) or associated data dictionaries available to external researchers. Any future data-sharing proposal would be considered on a case-by-case basis and would require appropriate authorization by the Sponsor and Data Protection Officer and compliance with applicable data-protection requirements.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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