Circuit-Guided Neuromodulation for Anorexia Nervosa

NCT07860320 | Not Yet Recruiting

• 3 other identifiers: RestrEAT7232092626CI_RESTREAT
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anorexia Nervosa

Keywords

Eating Disorders; Restrictive Eating; Brain Mapping; Personalized Neuromodulation; Functional Connectivity; Lesion Network Mapping; Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (4)

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

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

• Body Discrepancy Index After Stimulation

  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

  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

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

Other Outcomes (1)

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

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

Study Arms (3)

Intermittent Theta-Burst Stimulation (iTBS)

EXPERIMENTAL

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)

Continuous Theta-Burst Stimulation (cTBS)

EXPERIMENTAL

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)

Sham Theta-Burst Stimulation

SHAM COMPARATOR

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

Interventions

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.

Intermittent Theta-Burst Stimulation (iTBS)

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.

Continuous Theta-Burst Stimulation (cTBS)

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.

Sham Theta-Burst Stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Current manic or psychotic episode.
• Major or minor neurocognitive disorder.
• Neurodevelopmental disorder, including attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD).
• 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.

Sponsors & Collaborators

• Fundacao Champalimaud: lead

Study Sites (1)

Champalimaud Foundation

Lisbon, Lisbon District, 1400-038, Portugal

Location

Related Publications (20)

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MeSH Terms

Conditions

Anorexia Nervosa; Feeding and Eating Disorders

Condition Hierarchy (Ancestors)

Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Gonçalo Cotovio, MD, PhD

  Champalimaud Foundation

  PRINCIPAL INVESTIGATOR

• Albino J. Oliveira-Maia, MD, MPH, PhD

  Champalimaud Foundation

  STUDY DIRECTOR

Central Study Contacts

Gonçalo Cotovio, MD, PhD

CONTACT

+351 210 480 200; goncalo.cotovio@neuro.fchampalimaud.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors are masked to stimulation condition. The TMS operator is not masked and records the assigned stimulation condition in a restricted stimulation log that is not accessible to blinded outcome assessors. Unblinding is permitted only when required for a safety-related emergency.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant receives all three stimulation conditions (iTBS, cTBS, and sham) in randomized order across three separate crossover stimulation visits, with a washout interval of at least one week between visits. Each participant therefore serves as their own control.

Study Record Dates

• First Submitted: October 1, 2026
• First Posted: October 6, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)