This clinical trial aims to test the effects of fluvoxamine as a treatment for LongCOVID. Fluvoxamine is an FDA approved SSRI for Obsessive Compulsive Disorder (OCD), thathas already had success in preventing hospitalization in patients with COVID-19 (STOPCOVID and TOGETHER trials). This trial is testing whether fluoxamine helps to improvesymptoms and the negative impacts of long COVID in residents of Missouri and Illinois.
This clinical trial will test a promising drug for treatment of long COVID in 300 adults
who 1) are post-COVID-19 (at least 3 months since initial COVID symptoms and/or test
confirming SARS-CoV-2 infection); and 2) have evidence of neurocognitive Long COVID
(e.g., "brain fog", trouble concentrating, etc) which is causing suffering and/or
impairment. The trial will determine whether fluvoxamine (1) reduces long COVID symptoms,
2) improves cognitive performance. Fluvoxamine is an SSRI (FDA approved for OCD) that
also activates the sigma-1 receptor (an immunomodulatory receptor). It has been shown to
prevent clinical deterioration and hospitalization in outpatients with acute COVID-19
(STOP COVID and TOGETHER trials). For the current study, we will randomize participants
to fluvoxamine which is initially dosed at their preference, vs. placebo. This is done in
the following manner. First, each participant will receive an acute bout of fluvoxamine:
one dose of 25mg, then one dose of 50mg, then one dose of 100mg. We will assess their
subjective reaction to these test doses and use the information to randomize them to an
individually tailored course of fluvoxamine, vs. a matched placebo, for 16 weeks. The
benefits of this are (1) participants are more likely to accept randomization and
continue in the study if randomized to a dose they've already tested and accepted; (2)
participants' initial response, if any, to the acute dose may allow future
precision-medicine use of fluvoxamine, allowing physicians to give patients a test dose
and then a full trial preferentially to participants who are likely to respond. After the
randomized portion of the trial, participants will be given an opportunity to participate
in open-label treatment with fluvoxamine for 16 weeks. At the end of treatment, the study
medication will be tapered off over an approximate 1-2 week period, depending on the
final dose of study medication, and adjusted as appropriate if they experience
discontinuation symptoms. Outcome assessments will be a combination of patient-reported
assessments and validated neuropsychological tests.
Drug: Fluvoxamine
Fluvoxamine is an FDA approved drug for the treatment of OCD. This trial is testing the
effects of the drug on long COVID.
Inclusion Criteria:
1. Men and woman age 25 and older;
2. Not currently hospitalized
3. Participant self-report of past acute COVID episode with symptom onset and/or
initial positive test at least 3 months since initial COVID symptoms and/or test
confirming SARS-CoV-2 infection Note: Since some people with long COVID may not have
been able to obtain testing during the acute phase of illness, history of a positive
COVID-19 test is not required. We will collect data regarding the results of any
past COVID-19 testing, but this will not affect eligibility for the trial.
4. Currently symptomatic with self-reported worsening of cognitive function for at
least the past 2 months, that could not be better explained by other reasons (i.e.
alternative diagnosis or medication changes).
5. Able to provide informed consent.
6. Currently reside in Missouri or Illinois
Exclusion Criteria:
1. Illness severe enough to require hospitalization at the time of starting the study.
2. Unstable medical comorbidities (eg decompensated cirrhosis), per patient report
and/or medical records.
3. Immunocompromised from the following: solid organ transplant, BMT, high dose
steroids (>20mg prednisone per day), or tocilizumab
4. Already enrolled in another COVID 19 medication trial (not including vaccination or
prophylaxis trials)
5. Unable to provide informed consent
6. Unable to perform the study procedures, including not being a resident of the states
of Missouri or Illinois
7. Taking donepezil (rationale: donepezil is a S1R agonist), or sertraline (rationale:
sertraline is a strong sigma-1 antagonist).
8. Taking phenytoin (rationale: fluvoxamine inhibits its metabolism), clopidogrel
(rationale: fluvoxamine inhibits its metabolism from pro-drug to active drug which
raises risk of cardiovascular events), and St John's wort (rationale: fluvoxamine +
St John's wort are considered contraindicated because of the risk of serotonin
syndrome)
9. Taking SSRIs or SNRIs.
10. Individuals who report they have bipolar disorder or are taking medication for
bipolar disorder (lithium, valproate, high-dose antipsychotic), unless the
investigator concludes that the risk for mania is unlikely (ie it is doubtful that
the patient actually has bipolar disorder).
11. Individuals who take alprazolam or diazepam and are unwilling to cut the medication
by 25% (rationale: fluvoxamine modestly inhibits the metabolism of these drugs).
12. Participants taking theophylline, tizanidine, clozapine, or olanzapine (drugs with a
narrow therapeutic index that are primarily metabolized by CYP 1A2, which is
inhibited by fluvoxamine) will be reviewed with a study investigator and excluded
unless the investigator concludes that the risk to the participant is low (this
would be unlikely; example: participant takes tizanidine only as needed and is
willing to avoid it during study duration).
Washington University School of Medicine
Saint Louis, Missouri, United States
Eric Lenze, MD, Principal Investigator
Washington University School of Medicine