Vortioxetine for Post-COVID-19 Condition

November 29, 2024 updated by: Brain and Cognition Discovery Foundation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

149

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5S 1M2
        • Brain and Cognition Discovery Foundation (BCDF)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vortioxetine

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.
Drug: Vortioxetine

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.
Placebo Comparator: Placebo
Placebo capsule taken once daily for weeks 0-8.
Drug: Placebo
A placebo pill will be taken once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Weeks 0-8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline to Endpoint Change in World Health Organization Wellbeing Scale, 5-item (WHO-5)
Time Frame: Weeks 0-8
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)
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
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)
Week 0-8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brain and Cognition Discovery Foundation

Investigators

  • Principal Investigator: Roger S. McIntyre, MD, FRCPC, Brain and Cognition Discovery Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2021

Primary Completion (Actual)

February 22, 2023

Study Completion (Actual)

February 22, 2023

Study Registration Dates

First Submitted

September 12, 2021

First Submitted That Met QC Criteria

September 16, 2021

First Posted (Actual)

September 17, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

November 29, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCDF002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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