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Vortioxetine for Post-COVID-19 Condition

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05047952
Recruitment Status : Recruiting
First Posted : September 17, 2021
Last Update Posted : March 17, 2022
Sponsor:
Information provided by (Responsible Party):
Brain and Cognition Discovery Foundation

Brief 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 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.

Condition or disease Intervention/treatment Phase
Post-COVID-19 Condition Post-COVID-19 Syndrome Cognitive Impairment Drug: Vortioxetine Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons With Post-COVID-19 Condition
Actual Study Start Date : September 16, 2021
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Digit Symbol Substitution Test (DSST) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in Digit Symbol Substitution Test (DSST) (Pen/Paper Version and Online CogState Version as part of the CogState Online Cognitive Battery). Remote participants will not complete the pen/paper version of the DSST.


Secondary Outcome Measures :
  1. CogState Online Cognitive Battery [ Time Frame: Weeks 0-8 ]

    Baseline-to-endpoint (i.e., Week 8) change in CogState Online Cognitive Battery scores.

    The CogState Online Cognitive Battery (https://www.cogstate.com/) employed in the present trial will consist of four tests:

    1. Domain: Executive Function, Operation: Digit Symbol substitution test (CogState DSST)
    2. Domain: Attention, Operation: Operation: Choice Reaction Time (2 CogState tests: CogState Detection Test, CogState Identification Test)
    3. Domain: Memory, Operation: Visual Learning (CogState One Card Learning Test)

  2. Trails Making Test (TMT)-A/B [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Trails Making Test (TMT)-A/B will be used to assess change in cognitive function.

  3. Rey's auditory verbal learning test (RAVLT) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Rey's auditory verbal learning test (RAVLT) will be used to assess change in verbal memory.

  4. Perceived Deficits Questionnaire, 20-item (PDQ-20) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in Perceived Deficits Questionnaire, 20-item (PDQ-20) will be used to assess change in subjective cognitive functioning.

  5. Fatigue Severity Scale (FSS) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Fatigue Severity Scale (FSS) will be used to assess change in severity and impact of fatigue.

  6. Snaith Hamilton Pleasure Rating Scale (SHAPS) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Snaith Hamilton Pleasure Rating Scale (SHAPS) will be used to assess change in four domains of pleasure response/hedonic experience: interest/pastimes, social interaction, sensory experience, and food/drink.

  7. Patient Health Questionnaire, 9-item (PHQ-9) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Patient Health Questionnaire, 9-item (PHQ-9) will be used to assess change across self-rated depressive symptoms.

  8. Generalized Anxiety Scale, 7-item (GAD-7) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Generalized Anxiety Scale, 7-item (GAD-7) will be used to assess change across self-rated general anxiety symptoms.

  9. World Health Organization Wellbeing Scale, 5-item (WHO-5) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the World Health Organization Wellbeing Scale, 5-item (WHO-5) will be used to assess change in subjective well-being.

  10. EuroQol, 5-dimension, 5-level (EQ-5D-5L) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the EuroQol, 5-dimension, 5-level (EQ-5D-5L) will be used to assess change in quality of daily life across 5 dimensions (mobility, capacity for self-care, conduct of usual activities, pain/discomfort and anxiety/depression).

  11. Sheehan Disability Scale (SDS) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Sheehan Disability Scale (SDS) will be used to assess change in functional impairment due to disability.

  12. Post-Covid Functional Scale (PCFS) [ Time Frame: Weeks 0-8 ]
    Baseline-to-endpoint (i.e., Week 8) change in the Post-Covid Functional Scale (PCFS) will be used to assess change in functional status over time following COVID-19 infection.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05047952


Contacts
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Contact: Roger S. McIntyre, MD, FRCPC 647-450-8045 longcovid@bcdfoundation.ca
Contact: Mehala Subramaniapillai, MSc longcovid@bcdfoundation.ca

Locations
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Canada, Ontario
Brain and Cognition Discovery Foundation (BCDF) Recruiting
Toronto, Ontario, Canada, M5S 1M2
Contact: Roger McIntyre    647-450-8045    longcovid@bcdfoundation.ca   
Sponsors and Collaborators
Brain and Cognition Discovery Foundation
Investigators
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Principal Investigator: Roger S. McIntyre, MD, FRCPC Brain and Cognition Discovery Foundation
Additional Information:
Publications:

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Responsible Party: Brain and Cognition Discovery Foundation
ClinicalTrials.gov Identifier: NCT05047952    
Other Study ID Numbers: BCDF002
First Posted: September 17, 2021    Key Record Dates
Last Update Posted: March 17, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Brain and Cognition Discovery Foundation:
long COVID
post-acute COVID syndrome PASC
long haul COVID
COVID-19 sequelae
post-acute COVID-19 syndrome
chronic COVID syndrome
post-COVID-19 condition
long hauler
persistent COVID-19
vortioxetine
fatigue
brain fog
cognitive deficit
cognitive dysfunction
Trintellix
anti-inflammatory
Additional relevant MeSH terms:
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COVID-19
Syndrome
Disease
Pathologic Processes
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Vortioxetine
Antidepressive Agents
Psychotropic Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists