Post-COVID-19 ConditionPhase 2NCT05047952
Vortioxetine for Post-COVID-19 Condition
A Phase 2 study testing Vortioxetine in people with Post-COVID-19 Condition and Post-COVID-19 Syndrome, run by Brain and Cognition Discovery Foundation at 1 site in Canada.
Trial summary
A randomized, double-blinded, placebo-controlled trial will be conducted to evaluate vortioxetine, an antidepressant with established pro-cognitive properties, for the treatment of cognitive deficits which develop during or after an infection consistent with COVID-19, continue for 2+ months, and are not explained by… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-COVID-19 Condition, Post-COVID-19 Syndrome, Cognitive Impairment
- What is being tested?
- Vortioxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 149 participants
- Where
- 1 siteCanada
- Study dates
- 16 Sep 2021to 22 Feb 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18+
- Meets WHO-defined post-COVID-19 condition (WHO definition: 'Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.') To ensure the above criteria is met, participants will only be included in the study if they meet all eligibility criteria more than 12 weeks from the onset of their acute Covid-19 symptoms or positive PCR/antigen test.
- Documented history of SARS-CoV-2 infection (positive PCR/antigen test during acute illness OR clinical diagnosis by physician during or after the acute illness).
- Subjective cognitive complaints as detected by the Perceived Deficits Questionnaire (PDQ)-5.
- Ability to provide written informed consent.
- Resident of Canada.
Who cannot join
- Current symptoms are fully explained by major depressive disorder or bipolar disorder.
- Pre-existing conditions that may cause cognitive impairment, or symptoms similar to those seen in post-COVID-19 condition (e.g., major neurocognitive disorder, schizophrenia, chronic fatigue syndrome [CFS]/ encephalitis meningitis [EM]), as assessed by Mini International Neuropsychiatric Interview (MINI) 7.0.2.
- Inability to follow study procedures.
- Known intolerance to vortioxetine and/or prior trial of vortioxetine with demonstrated inefficacy.
- If participants are currently taking other antidepressants, they will be asked to discontinue the antidepressant for 2-4 weeks in order to participate in the study.
- Patients on other antidepressants are allowed to participate only if the antidepressant is prescribed at subtherapeutic doses for a primary indication other than mood disorders. Participants will be made aware in the consent form that the combination of the two antidepressants would be considered investigational and that the safety/efficacy profiles are unknown.
Show all 32Show fewer
- Current alcohol or substance use disorder.
- Inability to provide consent.
- Current alcohol and/or substance use disorder as confirmed by the M.I.N.I 7.0.2.
- Presence of comorbid psychiatric disorder that is a primary focus of clinical concern as confirmed by the M.I.N.I. 7.0.2.
- Medications approved and/or employed off-label for cognitive dysfunction (e.g., psychostimulants).
- Any medication for a general medical disorder that, in the opinion of the investigator, may affect cognitive function.
- Use of benzodiazepines within 12 hours of cognitive assessments.
- Consumption of alcohol within 8 hours of cognitive assessments.
- Physical, cognitive, or language impairments sufficient to adversely affect data derived from cognitive assessments.
- Diagnosed reading disability or dyslexia.
- Clinically significant learning disorder by history.
- Electroconvulsive therapy (ECT) in the last 6 months.
- History of moderate or severe head trauma (e.g., loss of consciousness for >1 hour), other neurological disorders, or unstable systemic medical diseases that in the opinion of the investigator are likely to affect the central nervous system.
- Pregnant and/or breastfeeding.
- Received investigational agents as part of a separate study within 30 days of the screening visit.
- Actively suicidal/presence of suicidal ideation or evaluated as being at suicide risk (as per clinical judgment).
- Currently receiving treatment with Monoamine Oxidase Inhibitors (MAOIs) antidepressants, antibiotics such as linezolid, or intravenous methylene blue.
- Previous hypersensitivity reaction to vortioxetine or any components of the formulation. Angioedema has been reported in patients treated with vortioxetine.
- Serotonin syndrome.
- Abnormal bleeding.
- Previous history of mania/hypomania.
- Angle closure glaucoma.
- Hyponatremia.
- Moderate hepatic impairment.
- Active seizure disorder/epilepsy, not controlled by medication
- Presence of any unstable medical conditions.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Brain and Cognition Discovery Foundation (BCDF)
Toronto, Ontario, M5S 1M2
About this study
Official title: Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons With Post-COVID-19 Condition
A randomized, double-blinded, placebo-controlled trial will be conducted to evaluate vortioxetine, an antidepressant with established pro-cognitive properties, for the treatment of cognitive deficits which develop during or after an infection consistent with COVID-19, continue for 2+ months, and are not explained by an alternative diagnosis (i.e., post-COVID-19 condition). Participants (aged 18-64 years) will receive vortioxetine (10-20 mg) or placebo for 8 weeks. Participants 65+ years will receive vortioxetine (5-10 mg) or placebo for 8 weeks. Changes in cognitive functioning from baseline to endpoint (week 8) will be assessed via the Digit Symbol Substitution Test (DSST). Study visits may be conducted remotely (e.g. via Zoom, by telephone), and/or in-person.
Read the detailed description
A significant percentage of individuals who have recovered from acute COVID-19 infection present with unabating, non-specific, distressing, and functionally impairing symptoms (i.e., post-COVID-19 condition). Commonly reported symptoms include, but are not limited to, cognitive impairment (e.g., "brain fog"), fatigue, apathy, depression, anxiety, insomnia, anergia, and loss of appetite. Toward the aim of identifying a common nomenclature and case definition, the World Health Organization (WHO) has recently proposed the moniker 'post COVID-19 condition'. It is estimated that approximately 10-30% of persons infected with COVID-19 experience characteristic symptoms persisting for more than 12 weeks following documentation of positive COVID-19 diagnosis.
Consensus exists that the phenomenology of post-COVID-19 condition is subserved by disturbance in immune-inflammatory systems. Currently, no treatment is identified as safe and effective for post-COVID-19 condition. A candidate treatment for post-COVID-19 condition should be capable of improving measures of cognitive function (i.e., objective and subjective), motivation and energy, as well as reducing fatigue. The rationale for prioritizing cognition as a primary therapeutic target is based on a concatenation of study results reporting that cognitive complaints/deficits and fatigue are some of the most common and debilitating features of post-COVID-19 condition. Preliminary evidence suggests that some antidepressants (e.g., SSRIs) are capable of reducing respiratory complications secondary to COVID-19 via putative mechanisms including, but not limited to, sigma-1 agonism and acid sphingomyelinase.
Vortioxetine is established as pro-cognitive, as evidenced by significant improvement on both subjective and objective measures. Vortioxetine is also documented to improve anticipatory and consummatory measures of reward function/anhedonia, improve general functioning, and measures of motivation and energy. Moreover, vortioxetine is not associated with emotional blunting and has preliminary evidence of improving sleep behaviour and circadian rhythms. The candidacy of vortioxetine as an effective treatment for post-COVID-19 condition is also strengthened by evidence indicating that vortioxetine exerts modulatory effects on cellular and cytokine systems known to be activated in persons with post-COVID-19 condition. Herein, we hypothesize that vortioxetine will be more effective than placebo in the treatment of cognitive impairment in persons with post-COVID-19 condition.
- Being tested
- Vortioxetine, Placebo
- Keywords
- vortioxetine, fatigue, long COVID, post-acute COVID syndrome PASC, long haul COVID, brain fog, cognitive deficit, cognitive dysfunction, COVID-19 sequelae, post-acute COVID-19 syndrome, Trintellix, chronic COVID syndrome, post-COVID-19 condition, long hauler, anti-inflammatory, persistent COVID-19
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Cognitive Dysfunction, Fatigue, Mental Fatigue, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VortioxetineDrug
Participants aged 18-64 years receiving vortioxetine will be provided 10 mg/day on days 1-14 of the treatment period, and will be titrated to 20 mg/day at the start of week 3 (day 15) based on study clinician judgment. For the remaining 6 weeks, the dose of vortioxetine will be 20 mg/day, unless adjudicated otherwise by a study clinician.
Per product monograph, participants aged 65+ years receiving vortioxetine will be provided 5 mg/day on days 1-14 of the treatment period, and will be titrated to 10 mg/day at the start of week 3 (day 15) based on study clinician judgment. For the remaining 6 weeks, the dose of vortioxetine will be 10 mg/day, unless adjudicated otherwise by a study clinician.
PlaceboDrug
A placebo pill will be taken once daily.
| Study group | Role | What they receive |
|---|---|---|
| Vortioxetine | Experimental | Participants aged 18-64 years: start at 10 mg vortioxetine once daily for the first 2 weeks, then dosed up to 20 mg vortioxetine once daily for weeks 2-8.
Participants aged 65+ years: start at 5 mg vortioxetine once daily for the first 2 weeks, then dosed up to 10 mg vortioxetine once daily for weeks 2-8. Receives: Drug: Vortioxetine |
| Placebo | Placebo comparator | Placebo capsule taken once daily for weeks 0-8. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Least Square Mean Change in Baseline to Week 8 on Z-score in Combined Digit Symbol Substitution Test (DSST)
This measures the least square mean change in baseline-to-end point on z-score on the combined DSST. Depicted is the least square (LS) mean [standard error of mean (SEM)] change in DSST z-scores from baseline to week 8 using an independent covariance matrix with time as a categorical variable, adjusted for the type of cognitive test (Pen/Paper versus Online CogState version). Larger least squares mean indicates a higher predicted or adjusted average outcome for that group or condition compared to others. In other words, if you have a higher least squares mean for a treatment group, it suggests that, after adjusting for the effects of other variables, that group tends to have a higher average outcome, indicating better performance. A least squares mean of 0 indicates that the groups has no difference in average outcome. There is no fixed maximum or minimum for LS Means. They are derived from the data and can, in principle, take any real value (positive, negative, or zero)
Measured: Weeks 0-8
Secondary outcomes (2)
Baseline to Endpoint Change in World Health Organization Wellbeing Scale, 5-item (WHO-5)
This measures the least square mean change in baseline-to-end point on scores on the WHO-5. Depicted is the least square (LS) mean [standard error of mean (SEM)] change in WHO-5 from baseline to week 8. Larger least squares mean indicates a higher predicted or adjusted average outcome for that group or condition compared to others. In other words, if you have a higher least squares mean for a treatment group, it suggests that, after adjusting for the effects of other variables, that group tends to have a higher average outcome, indicating better performance. A least squares mean of 0 indicates that the groups has no difference in average outcome. There is no fixed maximum or minimum for LS Means. They are derived from the data and can, in principle, take any real value (positive, negative, or zero)
Measured: Weeks 0-8
Baseline-to-endpoint (i.e., Week 8) Change in the Quick Inventory of Depressive Symptomology, Self Report (QIDS-SR-16)
This measures the least square mean change in baseline-to-end point on the QIDS-SR-16. A negative least squares estimate for the QIDS-SR-16 score from baseline to week 8 indicates a reduction in depressive symptoms. Specifically, it implies that, on average, the QIDS-SR-16 scores have decreased over the 8-week period. Since lower QIDS-SR-16 scores correspond to less severe depressive symptoms, a negative change is a positive outcome, showing improvement. A least squares mean of 0 indicates that the groups has no difference in average outcome. There is no fixed maximum or minimum for LS Means. They are derived from the data and can, in principle, take any real value (positive, negative, or zero)
Measured: Week 0-8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2021
- Study start16 Sep 2021
- Primary completion22 Feb 2023
- Study completion22 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Post-COVID-19 ConditionStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brain and Cognition Discovery Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roger S. McIntyre, MD, FRCPC, Principal investigator, Brain and Cognition Discovery Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05047952
- Sponsor's protocol ID
- BCDF002
- Status last verified
- Nov 2024
- First submitted
- 12 Sep 2021
- Last updated
- 16 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mahase E. Covid-19: What do we know about "long covid"? BMJ. 2020 Jul 14;370:m2815. doi: 10.1136/bmj.m2815. No abstract available.
PubMed 32665317Burke MJ, Del Rio C. Long COVID has exposed medicine's blind-spot. Lancet Infect Dis. 2021 Aug;21(8):1062-1064. doi: 10.1016/S1473-3099(21)00333-9. Epub 2021 Jun 18. No abstract available.
PubMed 34153235Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.
PubMed 32644129Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, Pujol JC, Klaser K, Antonelli M, Canas LS, Molteni E, Modat M, Jorge Cardoso M, May A, Ganesh S, Davies R, Nguyen LH, Drew DA, Astley CM, Joshi AD, Merino J, Tsereteli N, Fall T, Gomez MF, Duncan EL, Menni C, Williams FMK, Franks PW, Chan AT, Wolf J, Ourselin S, Spector T, Steves CJ. Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626-631. doi: 10.1038/s41591-021-01292-y. Epub 2021 Mar 10.
PubMed 33692530Mahase E. Long covid could be four different syndromes, review suggests. BMJ. 2020 Oct 14;371:m3981. doi: 10.1136/bmj.m3981. No abstract available.
PubMed 33055076Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, Shchendrygina A, Escher F, Vasa-Nicotera M, Zeiher AM, Vehreschild M, Nagel E. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Nov 1;5(11):1265-1273. doi: 10.1001/jamacardio.2020.3557.
PubMed 32730619Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, Miller JP, Yang L, Yingling M, Avidan MS, Reiersen AM. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020 Dec 8;324(22):2292-2300. doi: 10.1001/jama.2020.22760.
PubMed 33180097Hoertel N, Sanchez-Rico M, Vernet R, Beeker N, Jannot AS, Neuraz A, Salamanca E, Paris N, Daniel C, Gramfort A, Lemaitre G, Bernaux M, Bellamine A, Lemogne C, Airagnes G, Burgun A, Limosin F; AP-HP / Universities / INSERM COVID-19 Research Collaboration and AP-HP COVID CDR Initiative. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol Psychiatry. 2021 Sep;26(9):5199-5212. doi: 10.1038/s41380-021-01021-4. Epub 2021 Feb 4.
PubMed 33536545Christensen MC, Loft H, McIntyre RS. Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: A novel dual outcome measure in depressive disorders. J Affect Disord. 2018 Feb;227:787-794. doi: 10.1016/j.jad.2017.11.081. Epub 2017 Nov 16.
PubMed 29689693McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.
PubMed 27780334McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The Effects of Vortioxetine on Cognitive Function in Patients with Major Depressive Disorder: A Meta-Analysis of Three Randomized Controlled Trials. Int J Neuropsychopharmacol. 2016 Jun 15;19(10):pyw055. doi: 10.1093/ijnp/pyw055.
PubMed 27312740Cao B, Park C, Subramaniapillai M, Lee Y, Iacobucci M, Mansur RB, Zuckerman H, Phan L, McIntyre RS. The Efficacy of Vortioxetine on Anhedonia in Patients With Major Depressive Disorder. Front Psychiatry. 2019 Jan 31;10:17. doi: 10.3389/fpsyt.2019.00017. eCollection 2019.
PubMed 30766492Subramaniapillai M, Mansur RB, Zuckerman H, Park C, Lee Y, Iacobucci M, Cao B, Ho R, Lin K, Phan L, McIntyre RS. Association between cognitive function and performance on effort based decision making in patients with major depressive disorder treated with Vortioxetine. Compr Psychiatry. 2019 Oct;94:152113. doi: 10.1016/j.comppsych.2019.07.006. Epub 2019 Jul 24.
PubMed 31404802Fagiolini A, Florea I, Loft H, Christensen MC. Effectiveness of Vortioxetine on Emotional Blunting in Patients with Major Depressive Disorder with inadequate response to SSRI/SNRI treatment. J Affect Disord. 2021 Mar 15;283:472-479. doi: 10.1016/j.jad.2020.11.106. Epub 2020 Nov 19.
PubMed 33516560Cao B, Park C, Rosenblat JD, Chen Y, Iacobucci M, Subramaniapillai M, Mansur RB, Zuckerman H, Lee Y, McIntyre RS. Changes in sleep predict changes in depressive symptoms in depressed subjects receiving vortioxetine: An open-label clinical trial. J Psychopharmacol. 2019 Nov;33(11):1388-1394. doi: 10.1177/0269881119874485. Epub 2019 Sep 18.
PubMed 31530216
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons With Post-COVID-19 Condition
- ClinicalTrials.gov ID
- NCT05047952
- Acronym / sponsor ID
- BCDF002
- Keywords
- vortioxetine, fatigue, long COVID, post-acute COVID syndrome PASC, long haul COVID, brain fog, cognitive deficit, cognitive dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Brain and Cognition Discovery FoundationUniversity, hospital or other
- Study start
- 16 Sep 2021 (actual)
- Primary completion
- 22 Feb 2023 (actual)
- Study completion
- 22 Feb 2023 (actual)
- First posted
- 17 Sep 2021 (actual)
- Results
- Posted 16 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blinded, placebo-controlled trial will be conducted to evaluate vortioxetine, an antidepressant with established pro-cognitive properties, for the treatment of cognitive deficits which develop during or after an infection consistent with COVID-19, continue for 2+ months, and are not explained by an alternative diagnosis (i.e., post-COVID-19 condition). Participants (aged 18-64 years) will receive vortioxetine (10-20 mg) or placebo for 8 weeks. Participants 65+ years will receive vortioxetine (5-10 mg) or placebo for 8 weeks. Changes in cognitive functioning from baseline to endpoint (week 8) will be assessed via the Digit Symbol Substitution Test (DSST). Study visits may be conducted remotely (e.g. via Zoom, by telephone), and/or in-person.
Detailed description
A significant percentage of individuals who have recovered from acute COVID-19 infection present with unabating, non-specific, distressing, and functionally impairing symptoms (i.e., post-COVID-19 condition). Commonly reported symptoms include, but are not limited to, cognitive impairment (e.g., "brain fog"), fatigue, apathy, depression, anxiety, insomnia, anergia, and loss of appetite. Toward the aim of identifying a common nomenclature and case definition, the World Health Organization (WHO) has recently proposed the moniker 'post COVID-19 condition'. It is estimated that approximately 10-30% of persons infected with COVID-19 experience characteristic symptoms persisting for more than 12 weeks following documentation of positive COVID-19 diagnosis.
Consensus exists that the phenomenology of post-COVID-19 condition is subserved by disturbance in immune-inflammatory systems. Currently, no treatment is identified as safe and effective for post-COVID-19 condition. A candidate treatment for post-COVID-19 condition should be capable of improving measures of cognitive function (i.e., objective and subjective), motivation and energy, as well as reducing fatigue. The rationale for prioritizing cognition as a primary therapeutic target is based on a concatenation of study results reporting that cognitive complaints/deficits and fatigue are some of the most common and debilitating features of post-COVID-19 condition. Preliminary evidence suggests that some antidepressants (e.g., SSRIs) are capable of reducing respiratory complications secondary to COVID-19 via putative mechanisms including, but not limited to, sigma-1 agonism and acid sphingomyelinase.
Vortioxetine is established as pro-cognitive, as evidenced by significant improvement on both subjective and objective measures. Vortioxetine is also documented to improve anticipatory and consummatory measures of reward function/anhedonia, improve general functioning, and measures of motivation and energy. Moreover, vortioxetine is not associated with emotional blunting and has preliminary evidence of improving sleep behaviour and circadian rhythms. The candidacy of vortioxetine as an effective treatment for post-COVID-19 condition is also strengthened by evidence indicating that vortioxetine exerts modulatory effects on cellular and cytokine systems known to be activated in persons with post-COVID-19 condition. Herein, we hypothesize that vortioxetine will be more effective than placebo in the treatment of cognitive impairment in persons with post-COVID-19 condition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vortioxetine | Experimental | Drug: VortioxetineParticipants aged 18-64 years: start at 10 mg vortioxetine once daily for the first 2 weeks, then dosed up to 20 mg vortioxetine once daily for weeks 2-8. Participants aged 65+ years: start at 5 mg vortioxetine once daily for the first 2 weeks, then dosed up to 10 mg vortioxetine once daily for weeks 2-8. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsule taken once daily for weeks 0-8. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18+
- Meets WHO-defined post-COVID-19 condition (WHO definition: 'Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.') To ensure the above criteria is met, participants will only be included in the study if they meet all eligibility criteria more than 12 weeks from the onset of their acute Covid-19 symptoms or positive PCR/antigen test.
- Documented history of SARS-CoV-2 infection (positive PCR/antigen test during acute illness OR clinical diagnosis by physician during or after the acute illness).
- Subjective cognitive complaints as detected by the Perceived Deficits Questionnaire (PDQ)-5.
- Ability to provide written informed consent.
Key exclusion criteria (32 listed)
- Current symptoms are fully explained by major depressive disorder or bipolar disorder.
- Pre-existing conditions that may cause cognitive impairment, or symptoms similar to those seen in post-COVID-19 condition (e.g., major neurocognitive disorder, schizophrenia, chronic fatigue syndrome [CFS]/ encephalitis meningitis [EM]), as assessed by Mini International Neuropsychiatric Interview (MINI) 7.0.2.
- Inability to follow study procedures.
- Known intolerance to vortioxetine and/or prior trial of vortioxetine with demonstrated inefficacy.
- If participants are currently taking other antidepressants, they will be asked to discontinue the antidepressant for 2-4 weeks in order to participate in the study.
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 |
|---|---|---|
| VortioxetineParticipants aged 18-64 years receiving vortioxetine will be provided 10 mg/day on days 1-14 of the treatment period, and will be titrated to 20 mg/day at the start of week 3 (day 15) based on study clinician judgment. For the remaining 6 weeks, the dose of vortioxetine will be 20 mg/day, unless adjudicated otherwise by a study clinician. Per product monograph, participants aged 65+ years receiving vortioxetine will be provided 5 mg/day on days 1-14 of the treatment period, and will be titrated to 10 mg/day at the start of week 3 (day 15) based on study clinician judgment. For the remaining 6 weeks, the dose of vortioxetine will be 10 mg/day, unless adjudicated otherwise by a study clinician. | Drug | Vortioxetine |
| PlaceboA placebo pill will be taken once daily. | Drug | Placebo |
Primary outcome
Least Square Mean Change in Baseline to Week 8 on Z-score in Combined Digit Symbol Substitution Test (DSST)
Time frame: Weeks 0-8
This measures the least square mean change in baseline-to-end point on z-score on the combined DSST. Depicted is the least square (LS) mean [standard error of mean (SEM)] change in DSST z-scores from baseline to week 8 using an independent covariance matrix with time as a categorical variable, adjusted for the type of cognitive test (Pen/Paper versus Online CogState version). Larger least squares mean indicates a higher predicted or adjusted average outcome for that group or condition compared to others. In other words, if you have a higher least squares mean for a treatment group, it suggests that, after adjusting for the effects of other variables, that group tends to have a higher average outcome, indicating better performance. A least squares mean of 0 indicates that the groups has no difference in average outcome. There is no fixed maximum or minimum for LS Means. They are derived from the data and can, in principle, take any real value (positive, negative, or zero)
2 secondary outcomes
Baseline to Endpoint Change in World Health Organization Wellbeing Scale, 5-item (WHO-5)
Time frame: Weeks 0-8
Baseline-to-endpoint (i.e., Week 8) Change in the Quick Inventory of Depressive Symptomology, Self Report (QIDS-SR-16)
Time frame: Week 0-8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32665317Mahase E. Covid-19: What do we know about "long covid"? BMJ. 2020 Jul 14;370:m2815. doi: 10.1136/bmj.m2815. No abstract available.
- Background: PubMed 34153235Burke MJ, Del Rio C. Long COVID has exposed medicine's blind-spot. Lancet Infect Dis. 2021 Aug;21(8):1062-1064. doi: 10.1016/S1473-3099(21)00333-9. Epub 2021 Jun 18. No abstract available.
- Background: PubMed 32644129Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.
- Background: PubMed 33692530Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, Pujol JC, Klaser K, Antonelli M, Canas LS, Molteni E, Modat M, Jorge Cardoso M, May A, Ganesh S, Davies R, Nguyen LH, Drew DA, Astley CM, Joshi AD, Merino J, Tsereteli N, Fall T, Gomez MF, Duncan EL, Menni C, Williams FMK, Franks PW, Chan AT, Wolf J, Ourselin S, Spector T, Steves CJ. Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626-631. doi: 10.1038/s41591-021-01292-y. Epub 2021 Mar 10.
- Background: PubMed 33055076Mahase E. Long covid could be four different syndromes, review suggests. BMJ. 2020 Oct 14;371:m3981. doi: 10.1136/bmj.m3981. No abstract available.
- Background: PubMed 32730619Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, Shchendrygina A, Escher F, Vasa-Nicotera M, Zeiher AM, Vehreschild M, Nagel E. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Nov 1;5(11):1265-1273. doi: 10.1001/jamacardio.2020.3557.
- Background: PubMed 33180097Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, Miller JP, Yang L, Yingling M, Avidan MS, Reiersen AM. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020 Dec 8;324(22):2292-2300. doi: 10.1001/jama.2020.22760.
- Background: PubMed 33536545Hoertel N, Sanchez-Rico M, Vernet R, Beeker N, Jannot AS, Neuraz A, Salamanca E, Paris N, Daniel C, Gramfort A, Lemaitre G, Bernaux M, Bellamine A, Lemogne C, Airagnes G, Burgun A, Limosin F; AP-HP / Universities / INSERM COVID-19 Research Collaboration and AP-HP COVID CDR Initiative. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol Psychiatry. 2021 Sep;26(9):5199-5212. doi: 10.1038/s41380-021-01021-4. Epub 2021 Feb 4.
- Background: PubMed 29689693Christensen MC, Loft H, McIntyre RS. Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: A novel dual outcome measure in depressive disorders. J Affect Disord. 2018 Feb;227:787-794. doi: 10.1016/j.jad.2017.11.081. Epub 2017 Nov 16.
- Background: PubMed 27780334McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.
- Background: PubMed 27312740McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The Effects of Vortioxetine on Cognitive Function in Patients with Major Depressive Disorder: A Meta-Analysis of Three Randomized Controlled Trials. Int J Neuropsychopharmacol. 2016 Jun 15;19(10):pyw055. doi: 10.1093/ijnp/pyw055.
- Background: PubMed 30766492Cao B, Park C, Subramaniapillai M, Lee Y, Iacobucci M, Mansur RB, Zuckerman H, Phan L, McIntyre RS. The Efficacy of Vortioxetine on Anhedonia in Patients With Major Depressive Disorder. Front Psychiatry. 2019 Jan 31;10:17. doi: 10.3389/fpsyt.2019.00017. eCollection 2019.
- World Health Organization (WHO) COVID-19 DashboardLink provided by the sponsor.
- Rehabilitation in the wake of Covid-19 - A phoenix from the ashes; British Society of Rehabilitation Medicine (BSRM)Link provided by the sponsor.
- An Analysis of the Prolonged COVID-19 Symptoms Survey by Patient-Led Research TeamLink provided by the sponsor.
- Study With Vortioxetine on Emotional Functioning in Patients With Depression (COMPLETE)Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Post-COVID-19 Condition
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Not yet recruitingPhase 2
Study of VYD2311 for the Treatment of Adults With Long-COVID or Post-Vaccination Syndrome
Long COVID, COVID-19 (SARS-CoV-2 Infection)
Enrolling by invitationPhase 2
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
Systemic Inflammation, Neuroinflammation
Active, not recruitingObservational study
Pain in Long COVID-19: The Role of Sleep
Long COVID
RecruitingObservational study
Natural History of Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
Post-Coronavirus Disease 19
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. This study is not recruiting at the moment.
Roger S. McIntyre, MD, FRCPC principal investigator
Brain and Cognition Discovery Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vortioxetine in people with Post-COVID-19 Condition and Post-COVID-19 Syndrome, run by Brain and Cognition Discovery Foundation at 1 site in Canada.
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 6 inclusion and 32 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: finished, as of the sponsor's last update on 16 Jan 2025. 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 Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Least Square Mean Change in Baseline to Week 8 on Z-score in Combined Digit Symbol Substitution Test (DSST) (time frame: Weeks 0-8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05047952, which also lists 26 linked publications.
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 16 Jan 2025.