sElective Serotonin reuPtake inhibitoRs In posT-covid After COVID-19
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-70
SponsorAcademisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Fluvoxamine
DrugSubject 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.
Placebo
DrugSubject 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.
Treatment groups
160 Participants
are divided into 2 treatment groupsGroup A: Intervention armExperimental treatment 1 intervention
Group B: Control armPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
week 12Secondary outcomes
1
Fatigue severity
Dutch-Flemish Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue short form 8a. A higher scores indicates worse outcome.
Time frame
week 4, 8, 122
Cognitive functioning
Dutch-Flemish Patient-Reported Outcome Measurement Information System (PROMIS) cognitive function 8a. Higher scores indicate better functioning.
Time frame
week 4, 8, 123
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.
Time frame
week 4, 8, 124
PEM
DePaul Symptom Questionnaire (DSQ) Post Exertional Malaise (PEM). Higher scores indicate worse outcome.
Time frame
week 4, 8, 12Other outcomes
1
Biomarkers
(neuro) inflammation markers, corticoid receptor activity and cortisol, serotonin, IDO-2/ KP metabolites
Time frame
week 12Sponsors and contacts
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Source ClinicalTrials.gov