AzTrials
AzTrials

Long COVIDMALIBUNCT07278206

Brain Stimulation in Long COVID

A study testing Repetitive Transcranial Magnetic Stimulation in people with Long COVID and PASC Post Acute Sequelae of COVID 19, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Cognitive problems and severe fatigue are two frequently occurring symptoms in long COVID, also known as Post-Covid Condition or Post-Acute Sequelae of COVID-19 (PASC), and their causes are currently unknown. Previous studies have shown reduced blood flow and increased inflammation in the brains of people with PASC. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Repetitive Transcranial Magnetic Stimulation
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
66 participants
Where
1 siteNetherlands
Study dates
17 Nov 2025to 12 May 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Meet the World Health Organization (WHO) definition of long COVID.
  • Aged 18 years or older.
  • Severe fatigue, defined as a score ≥35 on the Checklist Individual Strength (CIS) fatigue subscale.
  • Significant cognitive complaints, defined as a score ≥18 on the CIS concentration subscale.
  • Commitment to actively undergo rTMS
  • Ability to attend the study site regularly for treatment sessions.
  • Capacity to provide written informed consent.

Who cannot join

  • Prior rTMS treatment or current intensive/experimental treatment for long COVID.
  • History of epilepsy or first-degree family history of epilepsy.
  • Recent initiation or dosage change of psychotropic medication (less than six weeks for psychotropic medication including antidepressants and antipsychotic drugs, less than two weeks for benzodiazepines). Medication doses must remain stable during the study.
  • Other active concurrent pharmacological treatments for post-covid symptoms
  • Contraindications to MRI scanning (e.g., non-removable metallic implants, severe claustrophobia).
  • Presence of a cochlear implant.
Show all 14Show fewer
  • Neurological disorders such as multiple sclerosis or other neurodegenerative conditions.
  • Pregnancy.
  • Known brain lesions or ischaemic scars influencing seizure threshold.
  • Severe uncontrolled migraines.
  • Severe cardiovascular disease
  • Raised intracranial pressure.
  • High alcohol consumption (males/females: 21/14 units per week) or use of epileptogenic drugs.
  • Severe sleep deprivation at the time of treatment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Céline N Dietz, MSc, MA contact

+31634010994

c.n.dietz@amsterdamumc.nl

Sander C.J. Verfaillie, Dr. contact

+31634005199

s.verfaillie@amsterdamumc.nl

Netherlands1 site, 1 recruiting

  • Amsterdam UMC

    Amsterdam

    Recruiting

Other trials in Netherlands

About this study

Official title: Mitigating Cognitive Problems and Fatigue With Brain Stimulation in Long COVID

Cognitive problems and severe fatigue are two frequently occurring symptoms in long COVID, also known as Post-Covid Condition or Post-Acute Sequelae of COVID-19 (PASC), and their causes are currently unknown. Previous studies have shown reduced blood flow and increased inflammation in the brains of people with PASC. These brain processes are related to fatigue and cognitive problems. In other conditions, these disrupted brain processes have been treated safely and successfully with non-invasive brain stimulation. This may offer an effective treatment for people with PASC.

The main goal of this clinical trial is to see whether non-invasive brain stimulation called repetitive transcranial magnetic stimulation (rTMS) can reduce fatigue in adults with PASC who also have trouble concentrating. rTMS uses short magnetic pulses on the scalp to gently stimulate a small brain area.

Read more

In this study, 66 adults with PASC will be included, recruited through the Post-COVID Network Netherlands. Participants will be randomly assigned to receive either active rTMS or sham (placebo) rTMS. Sham rTMS feels and looks similar to the active treatment, but it does not generate effective magnetic pulses. The brain area that will be targeted is personalized using a brain scan (MRI) during a planning task. All participants will receive 24 rTMS sessions over six weeks (four per week).

Fatigue will be measured within two weeks before and two weeks after treatment to determine whether active rTMS works better than sham. We will also look at cognition, brain connectivity and blood flow, signs of (neuro)inflammation, daily activity using an activity watch, and questionnaires about quality of life, mood, and sleep. Follow-up on cognition and questionnaires will take place 3 and 6 months after the end of the treatment.

Read the detailed description

Background Long COVID, also known as Post-COVID Condition (PCC) or Post-Acute Sequelae of COVID-19 (PASC), is characterized by persistent symptoms following SARS-CoV-2 infection without an alternative explanation. Fatigue and cognitive dysfunction are among the most common and disabling complaints, with substantial effects on daily functioning, work participation, and quality of life. Converging evidence from neuroimaging and fluid biomarkers points to altered cerebral perfusion, disrupted functional connectivity, and neuroinflammatory processes in at least a subset of people with PASC.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that can modulate cortical excitability and large-scale networks, with downstream effects on cerebral blood flow, connectivity and inflammatory signaling. Small, uncontrolled studies in PASC and related fatigue conditions suggest potential benefits of rTMS for fatigue and cognition, but placebo-controlled evidence in PASC is lacking and prior studies have used relatively few sessions. The present trial addresses this gap by testing a functional magnetic resonance (fMRI)-guided rTMS protocol in a randomized, double-blind design, while characterizing neurobiological mechanisms of change.

Objectives The primary objective is to determine whether high-frequency (10 Hz) rTMS reduces fatigue severity in adults with PASC compared with sham stimulation. Secondary objectives are to evaluate effects on physical and cognitive functioning, patient-reported outcome measures (e.g., mood, sleep, and quality of life), to quantify rTMS-related changes in neuroimaging and blood-based biomarkers reflecting neuronal integrity, cerebral perfusion, and (neuro)inflammation, and to examine whether these biomarkers can predict symptom improvement.

Design and procedures This is a single-center, randomized, double-blind, sham-controlled clinical trial. Sixty-six adults with PASC characterized by severe fatigue and cognitive complaints will be enrolled through the Post-COVID Network Netherlands. After baseline assessments, participants are randomized 1:1 to active rTMS or sham rTMS using block randomization implemented in Castor EDC with allocation concealment; participants and outcome assessors are blinded.

Treatment is delivered four times per week for six consecutive weeks (24 sessions). A minimum effective dose of 16 sessions applies when burden needs to be reduced. Outcome assessments are conducted within two weeks before the treatment at baseline (T0), within two weeks after the intervention period (T1), and at follow-up three months (T2) and six months (T3) after treatment to evaluate long-term effects. During the six-week intervention period a brief subset of patient-reported measures is collected weekly to monitor symptom trajectories and adverse effects.

Neuroimaging and blood sampling are obtained at T0 and T1. The MRI protocol (3T Siemens VIDA) includes structural, perfusion (ASL), resting-state and task-based fMRI (Tower of London), spectroscopy (MRS), and conventional FLAIR/SWI. Blood-derived biomarkers (e.g., NfL, GFAP, brain-derived tau, IL-6/IL-1/TNF-α, CCL11, BDNF) are assayed from EDTA plasma with standardized handling and storage prior to batch analysis. Actigraphy is assessed over 8 days prior to treatment and 8 days following treatment, and heart-rate variability is assessed during 4 nights and 4 times directly after waking for 5 minutes 2 weeks before treatment and directly after treatment.

Interventions Active treatment consists of high-frequency (10 Hz) rTMS delivered to the left dorsolateral prefrontal cortex at 110% resting motor threshold, with intensity adjusted for scalp-to-cortex distance. The stimulation target is individualized using task-based fMRI activation from a Tower of London planning task and neuronavigation (Localite). Sham sessions are performed with a placebo coil, that mimics sound and sensation, and at 60% motor threshold, so that it delivers no effective magnetic field. Participants and researchers involved in clinical assessments, data collection, and analysis remain blinded to allocation; technicians are trained to avoid any disclosure that could compromise masking. To enhance feasibility for participants with fatigue and sensory sensitivity, the treatment environment is kept low-stimulus with reduced lighting and noise, scheduling is flexible with a weekly buffer option, and the minimum 16-session option supports completion.

Endpoints and analysis The primary endpoint is change in fatigue from baseline to post-treatment, analyzed as the between-group difference in pre- to post-treatment change under the intention-to-treat principle. Secondary endpoints span cognitive functioning, mood, sleep, quality of life, and physical performance, together with multimodal neuroimaging and blood-based biomarkers that analyse neuronal integrity, cerebral blood flow, functional connectivity, and inflammation. Statistical analyses use linear mixed-effects models with appropriate covariates and multiplicity is handled via Bonferroni for secondary endpoints and FDR for neuroimaging and exploratory analyses.

Safety and ethics Safety is monitored throughout treatment and follow-up via standardized AE questionnaires and weekly tolerability questions. Known contraindications to rTMS/MRI are applied at screening, and procedures for managing common side effects and rare events are in place. The study is conducted per the Declaration of Helsinki and national regulations, with approval by the METc Amsterdam UMC. Participants provide written informed consent, travel costs are reimbursed, and a small participation compensation is provided.

Recruitment and setting Recruitment is coordinated through the Post Covid Network Netherlands patient portal, enabling efficient identification of potentially eligible individuals who consented to be approached for research. The trial is conducted at Amsterdam UMC.

Conclusion If the intervention proves effective, this study will provide the first placebo-controlled evidence for high-frequency rTMS to reduce fatigue in long COVID, with neuroimaging and blood biomarkers to shed light on underlying disease and treatment mechanisms. Even if no between-group difference is observed, the trial will yield valuable information on PASC and underlying mechanisms.

Being tested
Repetitive Transcranial Magnetic Stimulation, Sham device
Keywords
TMS, PASC, long COVID, PCC, neuroimaging, non-invasive brain stimulation, transcranial magnetic stimulation
Medical subject headings
Post-Acute COVID-19 Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Repetitive Transcranial Magnetic StimulationDevice

    Also called rTMS, TMS, non-invasive brain stimulation, NIBS

    The active intervention will consist of high-frequency (10 Hz) TMS delivered to the left dorsolateral prefrontal cortex (DLPFC), at 110% of the individual's resting motor threshold, adjusted for the individual cortex-skull distance, with 3,000 pulses per session with a total duration of 30 minutes (60 trains of 5 seconds, 25-second inter-train intervals). Sham-stimulation will be administered at 60% motor threshold at the same location (left DLPFC) using a placebo coil, which is identical to the stimulation coil in appearance, but with a built-in metal plate that blocks most of the active stimulation while maintaining mechanical scalp sensation. The stimulation target will be individualized using functional MRI data acquired during a Tower of London planning task allowing neuronavigation to the site of task-related activation. Each participant will receive four sessions per week for six weeks, totaling 24 sessions.

  • Sham deviceDevice

    Also called Sham rTMS, Sham TMS, Placebo, Placebo coil

    Sham-stimulation will be administered at 60% motor threshold at the left DLPFC using a placebo coil, which is identical to the stimulation coil in appearance, but with a built-in metal plate that blocks most of the active stimulation while maintaining mechanical scalp sensation. 3,000 pulses per session will be applied with a total duration of 30 minutes (60 trains of 5 seconds, 25-second inter-train intervals). The stimulation target will be individualized using functional MRI data acquired during a Tower of London planning task, allowing neuronavigation to the site of task-related activation. Each participant will receive four sessions per week for six weeks, totaling 24 sessions.

Study groups in NCT07278206
Study groupRoleWhat they receive
Active rTMSExperimentalThe active intervention will consist of high-frequency rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC). Stimulation will be administered at 10 Hz frequency, 110% of the individual's resting motor threshold and then adjusted for the individual cortex-skull distance, with 3,000 pulses per session with a total duration of 30 minutes (60 trains of 5 seconds, 25-second inter-train intervals).
Receives: Device: Repetitive Transcranial Magnetic Stimulation
Sham rTMSSham comparatorSham-stimulation will be administered at 60% motor threshold at the same location (left DLPFC) using a placebo coil, which is identical to the stimulation coil in appearance, but with a built-in metal plate that blocks most of the active stimulation while maintaining mechanical scalp sensation.
Receives: Device: Sham device

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fatigue

    Fatigue as measured by the 8-item fatigue subscale of the Checklist Individual Strength (CIS). The subscale is scored on a 7-point Likert scale, adding up to a total score between 8 and 56. A score of 35 or higher indicates the presence of severe fatigue.

    Measured: Fatigue will be measured within two weeks before and within two weeks after treatment, and at 3 and 6 months follow-up.

Secondary outcomes (30)

  1. Objective cognitive functioning

    Objective cognitive functioning will be measured using a composite score that combines the T-scores from multiple cognitive tests: (1) Stroop Test (information processing and interference sensitivity), (2) Trail Making Test A/B (various domains of executive function), (3) D2 Test (selective and sustained attention, concentration, and processing speed), and (4) 15-Word Test (memory).

    These scores will be combined into a composite score by taking the mean of the individual T-scores, which are corrected for age, sex, and education and will provide a comprehensive assessment of objective cognitive functioning. The final composite score will not include any individual test units but will provide an overall score reflecting performance across multiple cognitive domains.

    Measured: Objective cognitive functioning will be measured two weeks before and two weeks after treatment and at 3 and 6 months follow-up after treatment.

  2. Arterial Spin Labeling (ASL)

    We will measure blood-brain barrier integrity and perfusion using ASL.

    Measured: Neuroimaging will be performed within two weeks before and within two weeks after treatment.

  3. Magnetic Resonance Spectroscopy (MRS)

    Neuroinflammation and neuronal injury will be measured using MRS (metabolites for inflammation include choline, creatine and myo-inositol, and for neuronal injury N-acetyl-aspartate, glutamate and lactate).

    Measured: Neuroimaging will be performed within two weeks before and within two weeks after treatment.

  4. Functional Magnetic Resonance Imaging (fMRI)

    Participants will undergo a 10-minute resting-state scan, during which they are instructed to relax and remain awake while looking at a visual fixation cross for the entirety of the scan. After the resting-state scan, participants will complete the Tower of London task to measure task-based activity.

    Measured: Neuroimaging will be performed within two weeks before and within two weeks after treatment.

  5. Actigraphy

    Participants will wear an Actiwatch to monitor actigraphy for a continuous period of five days. Participants will be instructed to wear the actiwatch continuously during the measurement days and to maintain their usual daily routines. Actigraphy data will provide objective measures of day and nighttime activity.

    Measured: Continuous period of eight days two weeks before and directly after treatment

  6. Short physical performance battery (SPPB)

    The short physical performance battery (SPPB) will be performed to measure physical performance through three components: gait speed, balance, and repeated chair stands. The SPPB score is a composite of three physical tasks (gait speed, balance, and repeated chair stands) combined into a single score, ranging from 0-12. Higher scores mean better physical performance.

    Measured: Physical performance will be measured within two weeks before and within two weeks after treatment and at three and six months after treatment (follow-up).

  7. Simple Reaction Time (SRT)

    Reaction time will be assessed using a Simple Reaction Time (SRT) task, where participants are instructed to press the spacebar as quickly as possible when red circles appears on the screen. The task consists of 25 trials, with a randomized interval between each trial. The primary outcome will be the mean reaction time, with secondary analysis of the coefficient of variation (CV) across trials.

    Measured: Participants will complete the SRT within two weeks before, within two weeks after treatment and three and six months after treatment (follow-up).

  8. Effort-based decision task

    An effort-based decision task will be assessed to measure reward sensitivity. In this task, participants will either accept or reject offers in which they could exert physical effort (ticking boxes on screen, 5 levels) to gain rewards (money, 5 levels).

    Measured: The effort-based decision task will be completed within two weeks before and within two weeks after treatment.

  9. Neurofilament light (NF-L)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Neurofilament light (NF-L) will be quantified to reflect neuronal injury.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  10. Brain-Derived Tau (BD-Tau)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Brain-Derived Tau (BD-Tau) will be quantified to reflect neuronal injury.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  11. Interleukin-6 (IL-6)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis.Interleukin-6 (IL-6) will be quantified to measure (neuro)inflammation.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  12. Interleukin-1 (IL-1)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Interleukin-1 (IL-1) will be quantified to measure (neuro)inflammation.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  13. Glial Fibrillary Acidic Protein (GFAP)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Glial Fibrillary Acidic Protein (GFAP) will be quantified to measure astrocytic activity

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  14. Tumor Necrosis Factor-alpha (TNF-α)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Tumor Necrosis Factor-alpha (TNF-α) will be quantified to measure (neuro)inflammation.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  15. Eotaxin-1/CCL11

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Eotaxin-1/CCL11 will be quantified to measure (neuro)inflammation.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  16. Brain-derived neurotrophic factor (BDNF)

    Blood will be drawn from the antecubital vein into EDTA tubes, placed on ice, centrifuged, and plasma stored at -80°C until analysis. Brain-derived neurotrophic factor (BDNF) will be quantified as a brain plasticity marker.

    Measured: Blood samples will be collected within two weeks before and within two weeks after treatment.

  17. Checklist Individuele Spankracht (CIS)

    The Checklist Individuele Spankracht (CIS) measures subjective fatigue and related behavior. Score ranges from 20-140, with higher scores indicating worse outcomes.

    Measured: Survey will be completed within two weeks before and within two weeks after treatment, and three and six months after treatment (follow-up).

  18. Cognitive Failures Questionnaire (CFQ)

    The Cognitive Failures Questionnaire (CFQ) measures subjective cognition. Score ranges from 0-100, with higher scores indicating worse outcomes (greater cognitive failures).

    Measured: Survey will be completed within two weeks before and within two weeks after treatment, and three and six months after treatment (follow-up).

  19. Illness Perception Questionnaire (IPQ)-short form

    The Illness Perception Questionnaire (IPQ)-short form assesses various dimensions of an individual's illness perception, including its perceived consequences, timeline, controllability, and emotional representation. The responses to each question are evaluated individually, as no composite score is generated. Higher scores on each question indicate worse perceptions.

    Measured: Survey will be completed within two weeks before and within two weeks after treatment.

  20. Patient-Reported Outcomes Measurement Information System (PROMIS)

    The PROMIS-29 will measure a multi-domain scale that measures physical function, fatigue, pain interference, anxiety, depression, sleep disturbance, and ability to participate in social roles. The PROMIS-Cognitive function 8a will assess subjective cognitive function.

    For most PROMIS instruments, a score of 50 represents the average for the general U.S. population, with a standard deviation of 10. Higher T-scores reflect more of the concept being measured (e.g., higher cognitive function). For example, a T-score of 60 is one standard deviation above average (better than average) and a T-score of 40 is one standard deviation below average (worse than average).

    Measured: Survey will be completed within two weeks before treatment, weekly during treatment and within two weeks after treatment.

  21. Patient Health Questionnaire 9 (PHQ-9)

    The Patient Health Questionnaire 9 (PHQ-9) measures the severity of depressive symptoms, including mood and sleep. The score ranges from 0 to 27, with higher scores indicating worse outcomes. It includes a question specifically about suicidality (Item 9), which will be used to monitor thoughts of self-harm or suicide throughout the study.

    Measured: Survey will be completed within two weeks before treatment, weekly during treatment, within two weeks after treatment and at three and six months after treatment (follow-up).

  22. DePaul Symptom Questionnaire (DSQ)- post-exterional malaise and postural orthostatic tachycardia syndrome related questions

    Using the DePaul Symptom Questionnaire (DSQ) the severity of symptoms related to post-exertional malaise and postural orthostatic tachycardia syndrome will be assessed. Higher scores indicate worse outcomes (more severe symptoms).

    Measured: Survey will be completed within two weeks before treatment, within two weeks after treatment and at three and six months after treatment (follow-up).

  23. Bell Chronic Fatigue Syndrome Disability Scale

    The Bell chronic fatigue syndrome disability scale consists of one question that measures the degree of disability, focusing on the impact of the illness on daily functioning. A higher score means a greater degree of disability.

    Measured: Survey will be completed within two weeks before treatment, within two weeks after treatment and at three and six months after treatment (follow-up).

  24. Insomnia Severity Index (ISI)

    The insomnia severity index (ISI) evaluates the severity of insomnia symptoms, including difficulty falling asleep, staying asleep, and daytime impairment due to sleep problems. The score ranges from 0 to 28, with higher scores indicating worse outcomes.

    Measured: Survey will be completed within two weeks before treatment, within two weeks after treatment and at three and six months after treatment (follow-up).

  25. Jacobson Fatigue Catastrophizing Scale (J-FCS)

    The Jacobson Fatigue Catastrophizing Scale (J-FCS) assesses how individuals catastrophize or worry about their fatigue, including thoughts and feelings that amplify the experience of fatigue. The score ranges from 10 to 50, with higher scores indicating a higher degree of catastrophic thinking.

    Measured: Survey will be completed within two weeks before treatment and within two weeks after treatment.

  26. Self-Efficacy Scale 28 (SES-28)

    The Self-Efficacy Scale 28 (SES-28) consists of a 7-item questionnaire measuring self-efficacy and coping of difficult or stressful situations. The score ranges from 7 to 28, with higher scores reflecting a higher degree of self-efficacy.

    Measured: Survey will be completed within two weeks before treatment and within two weeks after treatment.

  27. Cognitive and Behavioral Responses to Symptoms Questionnaire (CBRQ)

    The Cognitive and Behavioral Responses to Symptoms Questionnaire (CBRQ) 16-item questionnaire is used to assess fear avoidance, damage beliefs, and all-or-nothing behavior. Items are scored on a 5-point scale, with higher scores indicating a stronger presence of the specific cognitive or behavioral response.

    Measured: Survey will be completed within two weeks before treatment and within two weeks after treatment.

  28. Treatment Inventory of Costs in Patients (TIC-P) - Work Absenteeism/Productivity Subscale

    The Treatment Inventory of Costs in Patients (TIC-P) - Work Absenteeism/Productivity Subscale assesses the impact of illness on work attendance and productivity. It does not provide a single score but instead measures whether the individual is currently working, whether they are required to stay home from work due to their condition, and how many days of work are missed due to illness. This information helps evaluate the effect of illness on work performance and productivity.

    Measured: Survey will be completed within two weeks before treatment and at three and six months after treatment (follow-up).

  29. Multimodal Evaluation of Sensory Sensitivity (MESSY) - multisensory, visual and auditory sensitivity subscales

    The Multimodal Evaluation of Sensory Sensitivity (MESSY) - multisensory, visual and auditory sensitivity subscales assess sensory sensitivity across these three sensory modalities. Every item is measured on a 1 to 5 point scale. A higher score indicates a higher sensory sensitivity severity.

    Measured: Survey will be completed within two weeks before treatment, within two weeks after treatment and three and six months after treatment (follow-up).

  30. Credibility Expectancy Questionnaire (CEQ)

    The Credibility Expectancy Questionnaire (CEQ) assesses the credibility and expectations of patients regarding the intervention, measuring how much they believe in its potential effectiveness. It consists of three questions regarding credibility and three questions regarding expectancy, each question rated or converted to a 9 point Likert scale. A higher score means higher treatment credibility and expectancy.

    Measured: Survey will be completed within two weeks before treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2025
  2. Study start17 Nov 2025
  3. Primary completion17 Nov 2028 (estimated)
  4. Study completion12 May 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07278206
Sponsor's protocol ID
NL-009207
Other IDs
11080022420018
Acronym
MALIBU
Status last verified
Dec 2025
First submitted
19 Nov 2025
Last updated
19 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zingaropoli MA, Pasculli P, Barbato C, Petrella C, Fiore M, Dominelli F, Latronico T, Ciccone F, Antonacci M, Liuzzi GM, Talarico G, Bruno G, Galardo G, Pugliese F, Lichtner M, Mastroianni CM, Minni A, Ciardi MR. Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19. Cells. 2023 Sep 13;12(18):2270. doi: 10.3390/cells12182270.

    PubMed 37759493

  • Yang G, Gu R, Kubo J, Kakuda W. Is the efficacy of repetitive transcranial magnetic stimulation influenced by baseline severity of fatigue symptom in patients with myalgic encephalomyelitis. Int J Neurosci. 2020 Jan;130(1):64-70. doi: 10.1080/00207454.2019.1663189. Epub 2019 Sep 13.

    PubMed 31483181

  • Verveen A, Verfaillie SCJ, Visser D, Koch DW, Verwijk E, Geurtsen GJ, Roor J, Appelman B, Boellaard R, van Heugten CM, Horn J, Hulst HE, de Jong MD, Kuut TA, van der Maaden T, van Os YMG, Prins M, Visser-Meily JMA, van Vugt M, van den Wijngaard CC, Nieuwkerk PT, van Berckel B, Tolboom N, Knoop H. Neuropsychological functioning after COVID-19: Minor differences between individuals with and without persistent complaints after SARS-CoV-2 infection. Clin Neuropsychol. 2025 Feb;39(2):347-362. doi: 10.1080/13854046.2024.2379508. Epub 2024 Jul 17.

    PubMed 39016843

  • Verveen A, Verfaillie SCJ, Visser D, Csorba I, Coomans EM, Koch DW, Appelman B, Barkhof F, Boellaard R, de Bree G, van de Giessen EM, Golla S, van Heugten CM, Horn J, Hulst HE, de Jong MD, Kuut TA, van der Maaden T, van Os YMG, Prins M, Slooter AJC, Visser-Meily JMA, van Vugt M, van den Wijngaard CC, Nieuwkerk PT, Knoop H, Tolboom N, van Berckel BNM. Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case-control study (VeCosCO). BMJ Open. 2023 Jun 30;13(6):e072611. doi: 10.1136/bmjopen-2023-072611.

    PubMed 37399444

  • van den Heuvel OA, Van Gorsel HC, Veltman DJ, Van Der Werf YD. Impairment of executive performance after transcranial magnetic modulation of the left dorsal frontal-striatal circuit. Hum Brain Mapp. 2013 Feb;34(2):347-55. doi: 10.1002/hbm.21443. Epub 2011 Nov 11.

    PubMed 22076808

  • Thaweethai T, Jolley SE, Karlson EW, Levitan EB, Levy B, McComsey GA, McCorkell L, Nadkarni GN, Parthasarathy S, Singh U, Walker TA, Selvaggi CA, Shinnick DJ, Schulte CCM, Atchley-Challenner R, Alba GA, Alicic R, Altman N, Anglin K, Argueta U, Ashktorab H, Baslet G, Bassett IV, Bateman L, Bedi B, Bhattacharyya S, Bind MA, Blomkalns AL, Bonilla H, Brim H, Bush PA, Castro M, Chan J, Charney AW, Chen P, Chibnik LB, Chu HY, Clifton RG, Costantine MM, Cribbs SK, Davila Nieves SI, Deeks SG, Duven A, Emery IF, Erdmann N, Erlandson KM, Ernst KC, Farah-Abraham R, Farner CE, Feuerriegel EM, Fleurimont J, Fonseca V, Franko N, Gainer V, Gander JC, Gardner EM, Geng LN, Gibson KS, Go M, Goldman JD, Grebe H, Greenway FL, Habli M, Hafner J, Han JE, Hanson KA, Heath J, Hernandez C, Hess R, Hodder SL, Hoffman MK, Hoover SE, Huang B, Hughes BL, Jagannathan P, John J, Jordan MR, Katz SD, Kaufman ES, Kelly JD, Kelly SW, Kemp MM, Kirwan JP, Klein JD, Knox KS, Krishnan JA, Kumar A, Laiyemo AO, Lambert AA, Lanca M, Lee-Iannotti JK, Logarbo BP, Longo MT, Luciano CA, Lutrick K, Maley JH, Mallett G, Marathe JG, Marconi V, Marshall GD, Martin CF, Matusov Y, Mehari A, Mendez-Figueroa H, Mermelstein R, Metz TD, Morse R, Mosier J, Mouchati C, Mullington J, Murphy SN, Neuman RB, Nikolich JZ, Ofotokun I, Ojemakinde E, Palatnik A, Palomares K, Parimon T, Parry S, Patterson JE, Patterson TF, Patzer RE, Peluso MJ, Pemu P, Pettker CM, Plunkett BA, Pogreba-Brown K, Poppas A, Quigley JG, Reddy U, Reece R, Reeder H, Reeves WB, Reiman EM, Rischard F, Rosand J, Rouse DJ, Ruff A, Saade G, Sandoval GJ, Santana JL, Schlater SM, Sciurba FC, Shepherd F, Sherif ZA, Simhan H, Singer NG, Skupski DW, Sowles A, Sparks JA, Sukhera FI, Taylor BS, Teunis L, Thomas RJ, Thorp JM, Thuluvath P, Ticotsky A, Tita AT, Tuttle KR, Urdaneta AE, Valdivieso D, VanWagoner TM, Vasey A, Verduzco-Gutierrez M, Wallace ZS, Ward HD, Warren DE, Weiner SJ, Welch S, Whiteheart SW, Wiley Z, Wisnivesky JP, Yee LM, Zisis S, Horwitz LI, Foulkes AS; RECOVER Consortium. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. 2023 Jun 13;329(22):1934-1946. doi: 10.1001/jama.2023.8823.

    PubMed 37278994

  • Schultheiss C, Willscher E, Paschold L, Gottschick C, Klee B, Henkes SS, Bosurgi L, Dutzmann J, Sedding D, Frese T, Girndt M, Holl JI, Gekle M, Mikolajczyk R, Binder M. The IL-1beta, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Rep Med. 2022 Jun 21;3(6):100663. doi: 10.1016/j.xcrm.2022.100663.

    PubMed 35732153

  • Scholing JM, Lambregts BIHM, van den Bosch R, Aarts E, van der Schaaf ME. Greater fatigue is more strongly associated with reduced reward sensitivity in the long-term phase of coronavirus disease (COVID-19) than in the early phase. Brain Behav Immun Health. 2025 Jul 5;48:101056. doi: 10.1016/j.bbih.2025.101056. eCollection 2025 Oct.

    PubMed 40686929

  • Sasaki N, Yamatoku M, Tsuchida T, Sato H, Yamaguchi K. Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction. Prog Rehabil Med. 2023 Feb 28;8:20230004. doi: 10.2490/prm.20230004. eCollection 2023.

    PubMed 36861061

  • Santana K, Franca E, Sato J, Silva A, Queiroz M, de Farias J, Rodrigues D, Souza I, Ribeiro V, Caparelli-Daquer E, Teixeira AL, Charvet L, Datta A, Bikson M, Andrade S. Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC). Brain Stimul. 2023 Jan-Feb;16(1):100-107. doi: 10.1016/j.brs.2023.01.1672. Epub 2023 Jan 21.

    PubMed 36693536

  • Sack AT, Cohen Kadosh R, Schuhmann T, Moerel M, Walsh V, Goebel R. Optimizing functional accuracy of TMS in cognitive studies: a comparison of methods. J Cogn Neurosci. 2009 Feb;21(2):207-21. doi: 10.1162/jocn.2009.21126.

    PubMed 18823235

  • Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

    PubMed 33243615

  • Reggente N, Moody TD, Morfini F, Sheen C, Rissman J, O'Neill J, Feusner JD. Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder. Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2222-2227. doi: 10.1073/pnas.1716686115. Epub 2018 Feb 12.

    PubMed 29440404

  • Peljto AL, Barker-Cummings C, Vasoli VM, Leibson CL, Hauser WA, Buchhalter JR, Ottman R. Familial risk of epilepsy: a population-based study. Brain. 2014 Mar;137(Pt 3):795-805. doi: 10.1093/brain/awt368. Epub 2014 Jan 26.

    PubMed 24468822

  • Pagliaccio D, Middleton R, Hezel D, Steinman S, Snorrason I, Gershkovich M, Campeas R, Pinto A, Van Meter P, Simpson HB, Marsh R. Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20346-20353. doi: 10.1073/pnas.1909199116. Epub 2019 Sep 23.

    PubMed 31548396

Questions about this trial

What is this clinical trial studying?

A study testing Repetitive Transcranial Magnetic Stimulation in people with Long COVID and PASC Post Acute Sequelae of COVID 19, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Céline N Dietz, MSc, MA (+31634010994, c.n.dietz@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fatigue (time frame: Fatigue will be measured within two weeks before and within two weeks after treatment, and at 3 and 6 months follow-up.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07278206, which also lists 30 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in