Post-COVIDPhase 3ESPRITNCT07359482
sElective Serotonin reuPtake inhibitoRs In posT-covid After COVID-19
A Phase 3 study testing Fluvoxamine in people with Post-COVID and POST-Covid 19, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Fatigue, cognitive problems, post-exertional malaise (PEM) and postural orthostatic tachycardia syndrome (POTS) are common and debilitating symptoms after COVID-19. The pathophysiology of post-COVID is not well understood and there is no established biomedical treatment. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post-COVID, POST-Covid 19, Post-COVID Conditions
- What is being tested?
- Fluvoxamine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteNetherlands
- Study dates
- 4 Jun 2026to 1 May 2028
- Phase
- Phase 3
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 to 70 years
- Severely fatigued (CIS fatigue score ≥ 35) at screening
- Fatigue started/increased significantly after Covid-19 (self-declared)
- Fatigue symptoms must be present for at least 3 months following the acute infection.
- Self-reported confirmation of having a SARS-CoV-2 infection by: Positive SARS-CoV-2 nucleic acid amplification test (NAAT), such as PCR; Positive SARS-CoV-2 rapid diagnostic test, including home-administered tests; COVID-19 diagnosis by a medical specialist (GP or in-hospital), based on the above or other clinical test or assessments. The above information will not be verified in medical records.
- Command of Dutch or English language to complete questionnaires
Show all 9Show fewer
- Able to participate in video calling.
- Willing and able to provide informed consent
- Allowing the trial team to exchange medical information that is relevant for the participants' safety and trial assessments with their GP and pharmacy.
Who cannot join
- Use of medication with interaction with fluvoxamine that cannot be discontinued
- Hospitalized in the acute phase of Covid-19
- Psychiatric/somatic disorders that could explain the severity of fatigue
- Neurodegenerative disorders (i.e. M Parkinson, Multiple sclerosis, M Alzheimer)
- Suicidality (current or recent) (according to WHO suicide screener)
- Starting or started with other medication intended to reduce post-covid symptoms during the last 2 months
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- Pregnancy (a positive urine or serum pregnancy test) or unwilling to use standard contraception
- Brugada- or Long QT interval syndrome
- epilepsy, porphyria, history of severe liver impairment
- known allergies to fluvoxamine or placebo/excipients
- known current alcohol or drug use problems.
- Bleeding disorders and past medical history of bleeding gastric or duodenal ulcers or other significant bleeding disorders
- claustrophobia (optional MRI substudy)
- having metal implants (optional MRI substudy)
- inability to lay still for 45 minutes (optional MRI substudy)
- Neurotrauma/ large stroke or brain abnormalities interfering with image analyses (optional MRI substudy)
- Inability to come to the Amsterdam UMC (optional MRI substudy).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam-Zuidoost, 1105 AZ
ESPRIT study team, +31204444100, ESPRIT-studie@amsterdamumc.nl
About this study
Official title: sElective Serotonin reuPtake inhibitoRs In posT-covid: ESPRIT
Fatigue, cognitive problems, post-exertional malaise (PEM) and postural orthostatic tachycardia syndrome (POTS) are common and debilitating symptoms after COVID-19. The pathophysiology of post-COVID is not well understood and there is no established biomedical treatment. Treatment options for post-COVID are thus much needed.
A promising candidate intervention is fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), that may reduce post-COVID symptoms because of its regulatory effect on the (neuro) immune system, the hypothalamic-pituitary-adrenal (HPA) axis and the tryptophan system. The investigators will randomize 160 participants to either fluvoxamine or placebo for 12 weeks.
The investigators will use advanced functional neuroimaging techniques during cognitive challenge (optional substudy) and plasma biomarkers (inflammatory markers, cortisol, serotonin, IDO-2 activity), to facilitate identifying potential mechanistic pathways of post -COVID treatment.
Read the detailed description
In this randomized placebo-controlled trial, the investigators will study the effectiveness of fluvoxamine in reducing fatigue severity (primary outcome), cognitive problems, PEM and POTS after 12 weeks of treatment in 160 post-COVID patients.
Moreover, the investigators will study treatment-emergent changes in plasma biomarkers, including blood-based neuro)inflammatory markers, cortisol, serotonin, aryl hydrocarbon receptor -indoleamine 2,3-dioxygenase-2 (IDO-2) and kynurenine pathway (KP) metabolites for potential mechanistic pathways of post-COVID treatment.
Numerous studies have indicated involvement of brain dysfunction in post COVID, which also relate to the degree of symptom severity (e.g. fatigue / cognitive problems). In an optional neuro-imaging sub-study, the investigators will use functional neuroimaging techniques with and without cognitive challenge to gain a better understanding of the brain functioning and structure in long COVID during fluvoxamine treatment versus placebo.
Objectives:
- To determine if fluvoxamine treatment (50 mg to 200 mg daily dosing) results in lower levels of fatigue severity than placebo after 12 weeks of treatment (primary).
- To determine if fluvoxamine treatment results in lower levels of PEM and POTS and a better cognitive functioning and health-related quality of life (HRQL) than placebo.
- To determine if changes in symptoms, i.e. fatigue severity, PEM, POTS, cognitive symptoms, are related to changes in biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2 -KP metabolites.
- To determine if biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2- KP metabolites, change from baseline to week 12 in participants who received fluvoxamine.
Optional Neuro-imaging sub-study:
-To determine which changes occur on functional brain imaging, brain metabolites and neuroinflammation during cognitive challenge and to determine if this brain response to cognitive challenge changes after fluvoxamine treatment versus placebo.
- Conditions
- Post-COVID, POST-Covid 19, Post-COVID Conditions
- Being tested
- Fluvoxamine, Placebo
- Keywords
- post-COVID, fluvoxamine, fatigue, biomarkers
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluvoxamineDrug
Subject are randomized in a double-blind manner (1:1 ratio) between fluvoxamine and placebo. During the first week subjects will receive a low dose daily dose of fluvoxamine of 25 mg or placebo. In the second week, subjects will receive a daily dose of 50 mg or placebo. From week 3 onwards, the fluvoxamine or placebo dose is increased by daily 50 mg every 6 days in a blinded manner but will not be further increased if participants are unwilling to accept a dose increase. For doses higher than 100 mg per day, dosing is done twice daily. The dose is increased to a maximum of 200 mg per day (i.e. 100 mg bid). The minimal daily dose is 50 mg.
PlaceboDrug
Subject are randomized in a double-blind manner (1:1 ratio) between fluvoxamine and placebo. During the first week subjects will receive a low dose daily dose of fluvoxamine of 25 mg or placebo. In the second week, subjects will receive a daily dose of 50 mg or placebo. From week 3 onwards, the fluvoxamine or placebo dose is increased by daily 50 mg every 6 days in a blinded manner but will not be further increased if participants are unwilling to accept a dose increase. For doses higher than 100 mg per day, dosing is done twice daily. The dose is increased to a maximum of 200 mg per day (i.e. 100 mg bid). The minimal daily dose is 50 mg.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Fluvoxamine. Receives: Drug: Fluvoxamine |
| Control arm | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue severity
Fatigue scale of the Checklist Individual Strength (CIS-20R). This scale has a minimum score of 8 and a maximum score of 56. High score indicate worse outcome.
Measured: week 12
Secondary outcomes (13)
Fatigue severity
Dutch-Flemish Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue short form 8a. A higher scores indicates worse outcome.
Measured: week 4, 8, 12
Cognitive functioning
Dutch-Flemish Patient-Reported Outcome Measurement Information System (PROMIS) cognitive function 8a. Higher scores indicate better functioning.
Measured: week 4, 8, 12
Cognitive functioning
Concentration score on the Checklist Individual Strength (CIS-20R). This scale has a minimum score of 5 and a maximum score of 35. A higher score indicates worse outcome.
Measured: week 4, 8, 12
PEM
DePaul Symptom Questionnaire (DSQ) Post Exertional Malaise (PEM). Higher scores indicate worse outcome.
Measured: week 4, 8, 12
POTS (National Aeronautics and Space Administration (NASA) lean test
NASA lean test
Measured: week 12
POTS
DePaul Symptom Questionnaire (DSQ) Postural Orthostatic Tachycardia Syndrome (POTS). Higher scores indicate worse outcome.
Measured: week 4, 8, 12
Health-related Quality of Life
Dutch-Flemish Patient-Reported Outcome Measurement Information System (PROMIS) Profile-29. Higher scores indicate better outcome.
Measured: week 4, 8, 12
Disability
Bell disability score. The minimum score is 0. The maximum score is 100. Higher scores indicate better outcome.
Measured: week 4, 8, 12
Side effects
Antidepressant Side Effect Checklist-21 (ASEC-21). Higher scores indicate worse outcome.
Measured: week 12
Side effects
Frequency, Intensity, Burden of Side Effects Rating scale (FIBSER scale). Higher scores indicate worse outcome.
Measured: week 12
Brain Perfusion (optional MRI substudy)
Arterial Spin Labeling
Measured: week 12
Brain functioning and connectivity (optional MRI substudy)
During resting-state and cognitive effort (challenging N-back (3-back vs. 0-back) on functional MRI
Measured: week 12
Brain metabolites and neuroinflammation (optional MRI substudy)
Magnetic Resonance Spectroscopy
Measured: week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study start4 Jun 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-COVIDStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two arm study in which post-COVID patients are randomly assigned to fluvoxamine or placebo in a double blind way.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pythia Nieuwkerk, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07359482
- Sponsor's protocol ID
- 2024-519540-32-00
- Other IDs
- 11080022420014
- Acronym
- ESPRIT
- Status last verified
- Jun 2026
- First submitted
- 14 Jan 2026
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Sharing will be in accordance with Dutch privacy laws and regulations.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- sElective Serotonin reuPtake inhibitoRs In posT-covid: ESPRIT
- ClinicalTrials.gov ID
- NCT07359482
- Acronym / sponsor ID
- ESPRIT / 2024-519540-32-00
- Conditions
- Post-COVID, POST-Covid 19, Post-COVID Conditions
- Keywords
- post-COVID, fluvoxamine, fatigue, biomarkers
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 4 Jun 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 22 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fatigue, cognitive problems, post-exertional malaise (PEM) and postural orthostatic tachycardia syndrome (POTS) are common and debilitating symptoms after COVID-19. The pathophysiology of post-COVID is not well understood and there is no established biomedical treatment. Treatment options for post-COVID are thus much needed.
A promising candidate intervention is fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), that may reduce post-COVID symptoms because of its regulatory effect on the (neuro) immune system, the hypothalamic-pituitary-adrenal (HPA) axis and the tryptophan system. The investigators will randomize 160 participants to either fluvoxamine or placebo for 12 weeks.
The investigators will use advanced functional neuroimaging techniques during cognitive challenge (optional substudy) and plasma biomarkers (inflammatory markers, cortisol, serotonin, IDO-2 activity), to facilitate identifying potential mechanistic pathways of post -COVID treatment.
Detailed description
In this randomized placebo-controlled trial, the investigators will study the effectiveness of fluvoxamine in reducing fatigue severity (primary outcome), cognitive problems, PEM and POTS after 12 weeks of treatment in 160 post-COVID patients.
Moreover, the investigators will study treatment-emergent changes in plasma biomarkers, including blood-based neuro)inflammatory markers, cortisol, serotonin, aryl hydrocarbon receptor -indoleamine 2,3-dioxygenase-2 (IDO-2) and kynurenine pathway (KP) metabolites for potential mechanistic pathways of post-COVID treatment.
Numerous studies have indicated involvement of brain dysfunction in post COVID, which also relate to the degree of symptom severity (e.g. fatigue / cognitive problems). In an optional neuro-imaging sub-study, the investigators will use functional neuroimaging techniques with and without cognitive challenge to gain a better understanding of the brain functioning and structure in long COVID during fluvoxamine treatment versus placebo.
Objectives:
- To determine if fluvoxamine treatment (50 mg to 200 mg daily dosing) results in lower levels of fatigue severity than placebo after 12 weeks of treatment (primary).
- To determine if fluvoxamine treatment results in lower levels of PEM and POTS and a better cognitive functioning and health-related quality of life (HRQL) than placebo.
- To determine if changes in symptoms, i.e. fatigue severity, PEM, POTS, cognitive symptoms, are related to changes in biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2 -KP metabolites.
- To determine if biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2- KP metabolites, change from baseline to week 12 in participants who received fluvoxamine.
Optional Neuro-imaging sub-study:
-To determine which changes occur on functional brain imaging, brain metabolites and neuroinflammation during cognitive challenge and to determine if this brain response to cognitive challenge changes after fluvoxamine treatment versus placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two arm study in which post-COVID patients are randomly assigned to fluvoxamine or placebo in a double blind way.
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Drug: FluvoxamineFluvoxamine. |
| Control arm | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adults aged 18 to 70 years
- Severely fatigued (CIS fatigue score ≥ 35) at screening
- Fatigue started/increased significantly after Covid-19 (self-declared)
- Fatigue symptoms must be present for at least 3 months following the acute infection.
- Self-reported confirmation of having a SARS-CoV-2 infection by: Positive SARS-CoV-2 nucleic acid amplification test (NAAT), such as PCR; Positive SARS-CoV-2 rapid diagnostic test, including home-administered tests; COVID-19 diagnosis by a medical specialist (GP or in-hospital), based on the above or other clinical test or assessments. The above information will not be verified in medical records.
Key exclusion criteria (17 listed)
- Use of medication with interaction with fluvoxamine that cannot be discontinued
- Hospitalized in the acute phase of Covid-19
- Psychiatric/somatic disorders that could explain the severity of fatigue
- Neurodegenerative disorders (i.e. M Parkinson, Multiple sclerosis, M Alzheimer)
- Suicidality (current or recent) (according to WHO suicide screener)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluvoxamineSubject are randomized in a double-blind manner (1:1 ratio) between fluvoxamine and placebo. During the first week subjects will receive a low dose daily dose of fluvoxamine of 25 mg or placebo. In the second week, subjects will receive a daily dose of 50 mg or placebo. From week 3 onwards, the fluvoxamine or placebo dose is increased by daily 50 mg every 6 days in a blinded manner but will not be further increased if participants are unwilling to accept a dose increase. For doses higher than 100 mg per day, dosing is done twice daily. The dose is increased to a maximum of 200 mg per day (i.e. 100 mg bid). The minimal daily dose is 50 mg. | Drug | Intervention arm |
| PlaceboSubject are randomized in a double-blind manner (1:1 ratio) between fluvoxamine and placebo. During the first week subjects will receive a low dose daily dose of fluvoxamine of 25 mg or placebo. In the second week, subjects will receive a daily dose of 50 mg or placebo. From week 3 onwards, the fluvoxamine or placebo dose is increased by daily 50 mg every 6 days in a blinded manner but will not be further increased if participants are unwilling to accept a dose increase. For doses higher than 100 mg per day, dosing is done twice daily. The dose is increased to a maximum of 200 mg per day (i.e. 100 mg bid). The minimal daily dose is 50 mg. | Drug | Control arm |
Primary outcome
Fatigue severity
Time frame: week 12
Fatigue scale of the Checklist Individual Strength (CIS-20R). This scale has a minimum score of 8 and a maximum score of 56. High score indicate worse outcome.
13 secondary outcomes
Fatigue severity
Time frame: week 4, 8, 12
Cognitive functioning
Time frame: week 4, 8, 12
Cognitive functioning
Time frame: week 4, 8, 12
PEM
Time frame: week 4, 8, 12
POTS (National Aeronautics and Space Administration (NASA) lean test
Time frame: week 12
POTS
Time frame: week 4, 8, 12
Health-related Quality of Life
Time frame: week 4, 8, 12
Disability
Time frame: week 4, 8, 12
Side effects
Time frame: week 12
Side effects
Time frame: week 12
Brain Perfusion (optional MRI substudy)
Time frame: week 12
Brain functioning and connectivity (optional MRI substudy)
Time frame: week 12
Brain metabolites and neuroinflammation (optional MRI substudy)
Time frame: week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Individual participant dataSharing planned: Yes. Sharing will be in accordance with Dutch privacy laws and regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fluvoxamine in people with Post-COVID and POST-Covid 19, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) 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 9 inclusion and 17 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 9 Jun 2026. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue severity (time frame: week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jun 2026.