Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons With Post-COVID-19 Condition
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 149
- 试验地点
- 1
- 主要终点
- Least Square Mean Change in Baseline to Week 8 on Z-score in Combined Digit Symbol Substitution Test (DSST)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Vortioxetine (Drug)
Placebo
Placebo capsule taken once daily for weeks 0-8.
干预措施: Placebo (Drug)
结局指标
主要结局
Least Square Mean Change in Baseline to Week 8 on Z-score in Combined Digit Symbol Substitution Test (DSST)
时间窗: 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)
次要结局
- Baseline to Endpoint Change in World Health Organization Wellbeing Scale, 5-item (WHO-5)(Weeks 0-8)
- Baseline-to-endpoint (i.e., Week 8) Change in the Quick Inventory of Depressive Symptomology, Self Report (QIDS-SR-16)(Week 0-8)