Vortioxetine for Post-COVID-19 Condition

Phase 2

Completed

• Conditions: Cognitive Impairment; Post-COVID-19 Syndrome; Post-COVID-19 Condition
• Interventions: Drug: Placebo; Drug: Vortioxetine

• Registration Number: NCT05047952
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2021-09-12
• Study Start: 2021-09-16
• Study First Submitted QC: 2021-09-16
• Study First Posted: 2021-09-17
• Primary Completion: 2023-02-22
• Study Completion: 2023-02-22
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo capsule taken once daily for weeks 0-8.
Vortioxetine	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.

Primary Outcome Measures

Name	Time	Method
Digit Symbol Substitution Test (DSST)	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

Name	Time	Method
Rey's auditory verbal learning test (RAVLT)	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.
Patient Health Questionnaire, 9-item (PHQ-9)	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.
Generalized Anxiety Scale, 7-item (GAD-7)	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.
Trails Making Test (TMT)-A/B	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.
Snaith Hamilton Pleasure Rating Scale (SHAPS)	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.
Perceived Deficits Questionnaire, 20-item (PDQ-20)	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.
World Health Organization Wellbeing Scale, 5-item (WHO-5)	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.
International Physical Activity Questionnaire (IPAQ)	Weeks 0-8	Baseline-to-endpoint (i.e., Week 8) change in the International Physical Activity Questionnaire (IPAQ) will be used to assess changes in various intensities of physical activity as well as sitting time weekly over time following COVID-19 infection.
CogState Online Cognitive Battery	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)
Effort-Expenditure for Rewards Task (EEfRT)	Week 0-8	Baseline-to-endpoint (i.e., Week 8) change in the Effort-Expenditure for Rewards Task (EEfRT) will be used to assess changes in motivation and reward over time following COVID-19 infection.
Fatigue Severity Scale (FSS)	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.
Sheehan Disability Scale (SDS)	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.
Behaviour Inhibition System/Behavioural Activation System (BIS/BAS)	Weeks 0-8	Baseline-to-endpoint (i.e., Week 8) change in the BIS/BAS will be used to assess change in the behavioral inhibition system and the behavioural activation system over time following COVID-19 infection.
Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR-16)	Week 0-8	Baseline-to-endpoint (i.e., Week 8) change in the Quick Inventory of Depressive Symptomology, Self Report (QIDS-SR-16) will be used to assess changes in severity of subjective depressive symptoms over time following COVID-19 infection.
EuroQol, 5-dimension, 5-level (EQ-5D-5L)	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).
Post-Covid Functional Scale (PCFS)	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.

Trial Locations

Locations (1)

Brain and Cognition Discovery Foundation (BCDF); 🇨🇦 Toronto, Ontario, Canada