Fluvoxamine maleate for Post-acute COVID-19 syndrome | Post-COVID syndrome

Inclusion criteria

• {"criterion_text":"- Adults aged 18 to 70 years\n- Severely fatigued (CIS fatigue score ≥ 35) at screening\n- Fatigue started/increased significantly after Covid-19 (self-declared)\n- Self-reported confirmation of having a SARS-CoV-2 infection by: •\tPositive SARS-CoV-2 nucleic acid amplification test (NAAT), such as PCR; •\tPositive SARS-CoV-2 rapid diagnostic test, including home-administered tests; •\tCOVID-19 diagnosis by a medical specialist (GP or in-hospital), based on the above or other clinical test or assessments.\n- Command of Dutch or English language to complete questionnaires\n- Able to participate in video calling\n- Willing and able to provide informed consent\n- 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

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

Primary endpoints

• {"endpoint_text":"- Fatigue severity (Checklist Individual Strength (CIS-20R) fatigue score) at week 12","definition_or_measurement_approach":"Measured using the Checklist Individual Strength (CIS-20R) fatigue score at week 12."}

Secondary endpoints

• {"endpoint_text":"- Fatigue severity (PROMIS fatigue 8)","definition_or_measurement_approach":"Measured using the PROMIS Fatigue 8-item instrument."}
• {"endpoint_text":"- Cognitive functioning (PROMIS) cognitive function 8a, CIS-20R concentration score)","definition_or_measurement_approach":"Measured using PROMIS Cognitive Function 8a and CIS-20R concentration score."}
• {"endpoint_text":"- Post Exertional Malaise (PEM) (DePaul Symptom Questionnaire (DSQ-PEM)","definition_or_measurement_approach":"Measured using the DePaul Symptom Questionnaire (DSQ-PEM)."}
• {"endpoint_text":"- Postural Orthostatic Tachycardia Syndrome (POTS) National Aeronautics and Space Administration (NASA) lean test and DSQ-POTS)","definition_or_measurement_approach":"Assessed using the NASA lean test and DSQ-POTS instruments."}
• {"endpoint_text":"- Health-related quality of life (HRQL) (PROMIS-29, Bell disability scale))","definition_or_measurement_approach":"Measured using PROMIS-29 and the Bell disability scale."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Safety and tolerability assessed with ASEC-21, FIBSER scale, and DESS scale for withdrawal symptoms."}
• {"endpoint_text":"- Biomarkers ((neuro) inflammation makers, glucocorticoid receptor (GR) activity, cortisol, serotonin, IDO-2 -kynurenine pathway (KP) metabolites).","definition_or_measurement_approach":"Changes in biomarkers including (neuro)inflammation markers, GR activity, cortisol, serotonin, and IDO-2 KP metabolites measured from baseline to week 13."}
• {"endpoint_text":"- Neuro-imaging substudy: Perfusion (Arterial Spin Labeling MRI)","definition_or_measurement_approach":"Perfusion assessed by Arterial Spin Labeling MRI in the neuro-imaging substudy."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Brain function and connectivity assessed with fMRI during resting-state and an N-back cognitive challenge (3-back vs 0-back)."}
• {"endpoint_text":"- Neuro-imaging substudy: brain metabolites and neuroinflammation (Magnetic Resonance Spectroscopy)","definition_or_measurement_approach":"Brain metabolites and neuroinflammation assessed using Magnetic Resonance Spectroscopy."}

Netherlands

Earliest CTIS Part Ii Submission Date

14-10-2025

Latest Decision Or Authorization Date

08-04-2026

Processing Time Days

176

Number Of Sites

1

Number Of Participants

160

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"ZonMw","duties_or_roles":"Monetary support","organisation_type":""}