ESPRIT study

2024-519540-32-00 Phase III and Phase IV (Integrated) Ongoing, recruiting

Start 6 May 2026 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Phase III and Phase IV (Integrated)
Status Ongoing, recruiting
Participants planned 160
Countries 1
Sites 1

post COVID

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.

Key facts

Sponsor
Amsterdam UMC Stichting
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Virus Diseases [C02]
Trial duration
6 May 2026 → ongoing
Decision date (initial)
2025-11-17
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
ZonMw

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

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.

Secondary objectives 4

  1. To determine if fluvoxamine treatment results in lower levels of post exertional malaise (PEM) and postural orthostatic tachycardia syndrome (POTS) and a better cognitive functioning and health-related quality of life (HRQL) than placebo.
  2. 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 kynurenine pathway (KP) metabolites.
  3. To determine if biomarkers, i.e., (neuro)inflammation markers, cortisol, serotonin and IDO-2- KP metabolites, change from baseline to week 13 in participants who received fluvoxamine.
  4. 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 and MedDRA coding

post COVID

VersionLevelCodeTermSystem organ class
28.0 LLT 10085505 Post-COVID syndrome 100000004848
28.0 PT 10085503 Post-acute COVID-19 syndrome 100000004862
28.0 LLT 10085867 Post-COVID-19 syndrome 100000004848

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Adults aged 18 to 70 years
  2. Severely fatigued (CIS fatigue score ≥ 35) at screening
  3. Fatigue started/increased significantly after Covid-19 (self-declared)
  4. 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.
  5. Command of Dutch or English language to complete questionnaires
  6. Able to participate in video calling
  7. Willing and able to provide informed consent
  8. Allowing the trial team to exchange medical information that is relevant for the participants’ safety and trial assessments with their general practitioner and pharmacy.

Exclusion criteria 18

  1. Use of medication with interaction with fluvoxamine that cannot be discontinued
  2. known allergies to fluvoxamine or placebo/excipients
  3. known current alcohol or drug use problems
  4. Bleeding disorders and past medical history of bleeding gastric or duodenal ulcers or other significant bleeding disorders
  5. Additional exclusion criteria optional neuro-imaging sub-study: claustrophobia
  6. Additional exclusion criteria optional neuro-imaging sub-study: having metal implants
  7. Additional exclusion criteria optional neuro-imaging sub-study: inability to lay still for 45 minutes
  8. Additional exclusion criteria optional neuro-imaging sub-study: Neurotrauma/ large stroke or brain abnormalities interfering with image analyses
  9. Additional exclusion criteria optional neuro-imaging sub-study: Inability to come to the Amsterdam UMC
  10. Hospitalized in the acute phase of Covid-19
  11. Psychiatric/somatic disorders that could explain the severity of fatigue
  12. Neurodegenerative disorders (i.e. M Parkinson, Multiple sclerosis, M Alzheimer)
  13. Suicidality (current or recent) (according to validated WHO suicide screener)
  14. Starting or started with other medication intended to reduce post-covid symptoms during the last 2 months
  15. Pregnancy (a positive urine or serum pregnancy test)/ unwilling to use standard contraception
  16. Brugada- or Long QT interval syndrome
  17. epilepsy, porphyria, history of severe liver impairment
  18. • Clinical laboratory test results at the baseline visit requiring immediate medical attention (refer to Appendix 6 and 7).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Fatigue severity (Checklist Individual Strength (CIS-20R) fatigue score) at week 12

Secondary endpoints 10

  1. Fatigue severity (PROMIS fatigue 8)
  2. Cognitive functioning (PROMIS) cognitive function 8a, CIS-20R concentration score)
  3. Post Exertional Malaise (PEM) (DePaul Symptom Questionnaire (DSQ-PEM)
  4. Postural Orthostatic Tachycardia Syndrome (POTS) National Aeronautics and Space Administration (NASA) lean test and DSQ-POTS)
  5. Health-related quality of life (HRQL) (PROMIS-29, Bell disability scale))
  6. Side effects, (Antidepressant Side Effect Checklist-21 (ASEC-21) and Frequency, Intensity, Burden of Side Effects Rating scale (FIBSER scale), withdrawal symptoms (Discontinuation- Emergent Signs and Symptoms (DESS) Scale)
  7. Biomarkers ((neuro) inflammation makers, glucocorticoid receptor (GR) activity, cortisol, serotonin, IDO-2 -kynurenine pathway (KP) metabolites).
  8. Neuro-imaging substudy: Perfusion (Arterial Spin Labeling MRI)
  9. Neuro-imaging substudy: brain functioning and connectivity during resting-state and cognitive effort (challenging N-back (3-back vs. 0-back) with functional Magnetic Resonance Imaging (fMRI)
  10. Neuro-imaging substudy: brain metabolites and neuroinflammation (Magnetic Resonance Spectroscopy)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Fluvoxamine 50 mg film-coated tablets

PRD10021563 · Product

Active substance
Fluvoxamine Maleate
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
200 mg milligram(s)
Max total dose
200 mg/l milligram(s)/litre
Max treatment duration
13 Week(s)
Authorisation status
Authorised
ATC code
N06AB08 — FLUVOXAMINE
Marketing authorisation
PL 11311/0488
MA holder
TILLOMED LABORATORIES LTD
MA country
XI
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
Route of administration
ORAL
Max daily dose
200 mg milligram(s)
Max total dose
200 mg milligram(s)
Max treatment duration
12 Week(s)
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

75 Total trials 44 Recruiting 14 Ended
Academic / Non-commercial
Sponsor organisation
Amsterdam UMC Stichting
Address
De Boelelaan 1117
City
Amsterdam
Postcode
1081 HV
Country
Netherlands

Scientific contact point

Organisation
Amsterdam UMC Stichting
Contact name
Pythia Nieuwkerk

Public contact point

Organisation
Amsterdam UMC Stichting
Contact name
Pythia Nieuwkerk

Sponsor responsibilities

Article 77 compliance
Amsterdam UMC Stichting
Contact point sponsor
Amsterdam UMC Stichting
Article 77 implementation
Amsterdam UMC Stichting

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 160 1
Rest of world — 0 —

Investigational sites

Netherlands

1 site · Ongoing, recruiting
Amsterdam UMC Research B.V.
Medical Psychology, Meibergdreef 9, 1105 AZ, Amsterdam

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2026-05-06 2026-05-06

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-519540-32-00 clean redacted 1.1
Protocol (for publication) D1_Protocol 2024-519540-32-00_clean_redacted 2
Protocol (for publication) D4_NL ENG Patient facing documents questionnaire DESS 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire FIBSER schaal 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire ASEC-21 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire Bell-Functionaliteits-Schaal 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire CIS concentratie schaal 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire CIS vermoeidheid schaal 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire DSQ_PEM 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire DSQ_POTS 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire PROMIS SF Cognitive Function 8a_DUT_FLE 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire PROMIS SF Fatigue 8a_DUT_FLE 1
Protocol (for publication) D4_NL NL Patient facing documents questionnaire PROMIS-29 Profile DUT-FLE 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_ NL-NL_SIS and ICF_clean redacted 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC fluvoxamine 1
Synopsis of the protocol (for publication) D1_Protocol synopsis NL NL 2024-519540-32-00 2

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-07-25 Netherlands Acceptable
2025-11-10
 2025-11-17
2 SUBSTANTIAL MODIFICATION SM-1 2026-03-12 Netherlands Acceptable
2026-04-08
 2026-04-08

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