Cognitive Impairment Clinical Trial
Official title:
Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons With Post-COVID-19 Condition
Verified date | May 2023 |
Source | Brain and Cognition Discovery Foundation |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 200 |
Est. completion date | February 22, 2023 |
Est. primary completion date | February 22, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Canada | Brain and Cognition Discovery Foundation (BCDF) | Toronto | Ontario |
Lead Sponsor | Collaborator |
---|---|
Brain and Cognition Discovery Foundation |
Canada,
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* Note: There are 21 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Digit Symbol Substitution Test (DSST) | 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. | Weeks 0-8 | |
Secondary | CogState Online Cognitive Battery | 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: Domain: Executive Function, Operation: Digit Symbol substitution test (CogState DSST) Domain: Attention, Operation: Operation: Choice Reaction Time (2 CogState tests: CogState Detection Test, CogState Identification Test) Domain: Memory, Operation: Visual Learning (CogState One Card Learning Test) |
Weeks 0-8 | |
Secondary | Trails Making Test (TMT)-A/B | 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. | Weeks 0-8 | |
Secondary | Rey's auditory verbal learning test (RAVLT) | 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. | Weeks 0-8 | |
Secondary | Perceived Deficits Questionnaire, 20-item (PDQ-20) | 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. | Weeks 0-8 | |
Secondary | Fatigue Severity Scale (FSS) | 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. | Weeks 0-8 | |
Secondary | Snaith Hamilton Pleasure Rating Scale (SHAPS) | 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. | Weeks 0-8 | |
Secondary | Patient Health Questionnaire, 9-item (PHQ-9) | 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. | Weeks 0-8 | |
Secondary | Generalized Anxiety Scale, 7-item (GAD-7) | 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. | Weeks 0-8 | |
Secondary | World Health Organization Wellbeing Scale, 5-item (WHO-5) | 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. | Weeks 0-8 | |
Secondary | EuroQol, 5-dimension, 5-level (EQ-5D-5L) | 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). | Weeks 0-8 | |
Secondary | Sheehan Disability Scale (SDS) | 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. | Weeks 0-8 | |
Secondary | Post-Covid Functional Scale (PCFS) | 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. | Weeks 0-8 | |
Secondary | Behaviour Inhibition System/Behavioural Activation System (BIS/BAS) | 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. | Weeks 0-8 | |
Secondary | International Physical Activity Questionnaire (IPAQ) | 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. | Weeks 0-8 | |
Secondary | Effort-Expenditure for Rewards Task (EEfRT) | 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. | Week 0-8 | |
Secondary | Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR-16) | 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. | Week 0-8 |
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