Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID
- Conditions
- Long COVIDSars-CoV-2 InfectionCoronavirus InfectionsCOVID-19
- Interventions
- Other: Placebo
- Registration Number
- NCT06631287
- Lead Sponsor
- Wes Ely
- Brief Summary
The overarching goal of this study is to determine if baricitinib, as compared to placebo, will improve neurocognitive function, along with measures of physical function, quality of life, post-exertional malaise, effect of breathlessness on daily activities, post-COVID-19 symptom burden, and biomarkers of inflammation and viral measures, in participants with Long COVID.
- Detailed Description
Since the emergence of the severe acute respiratory syndrome coronavirus 2 pathogen in late 2019, there have been over 680 million cases worldwide and over 6 million deaths. In the United States alone, there have been over 100 million cases and over 1 million deaths. Both novel vaccines and effective therapeutics have helped reduce mortality in well-resourced countries. Despite these advances, millions of patients subsequently experience a devastating post-acute infection syndrome known as post-acute sequelae of SARS-CoV-2 infection (PASC), or better known by patients as Long COVID (LC). In the United States alone, it is estimated that up to 18 million adults suffer from LC with persistent neurocognitive impairments (NCI) and cardiopulmonary symptoms such as dyspnea and exercise intolerance for months to years after acute COVID-19. Additionally, up to 1 in 5 patients who were working prior to contracting SARS-CoV-2 may not return to the workforce due to cognitive and physical impairments. The public health burden of LC is estimated to be the largest seen from an emerging disease in the last 100 years, yet there are currently no effective interventions.
These clear and objective changes in cognitive function and brain structure highlight the devastating and long-lasting effects of SARS-CoV-2 infection on survivors' long-term health, highlighting the need for effective therapies to improve long-term cognitive outcomes.
In addition to the devastating NCI that patients with LC experience, many survivors go on to experience activity-limiting dyspnea on exertion, exercise intolerance, and reduced physical function. In fact, patients who have not fully recovered physically 5 months after infection may fail to recover further by one year. Patients with LC experience significant self-reported physical symptoms including persistent fatigue and dyspnea as well as objective impairments in exercise capacity and physical function upon performance testing. These impairments, in addition to cognitive function and mental health, lead to significant reductions in quality of life for these survivors.
While viral reservoirs, systemic and organ-level inflammation are leading hypotheses for the mechanistic underpinnings of LC, no trials to date have investigated the use of agents targeting these mechanisms. Similar chronic inflammation plays a crucial role in the increased risk of cardiovascular disease (CVD) and NCI for people with HIV (PWH) as indicated by elevated soluble and cellular markers of inflammation, endothelial dysfunction, and hypercoagulability in this population. Activation of the Janus kinase (JAK)-STAT pathway, which drives a proinflammatory milieu, has been reported during HIV infection and is associated with CVD, NCI, and HIV persistence. Even in the absence of a viral infection, these same conditions and comorbidities are driven by a very similar chronic inflammatory state.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 550
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Baricitinib Baricitinib Janus kinase inhibitor Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method CNS-Vital Signs Global Cognitive Index Month 6 Objective neuropsychological function determined using the CNS-Vital Signs Global Cognitive Index between study arms at 6-months, adjusted for baseline.
CNS-Vital Signs Global Cognitive Index subscale is an average score derived from the domain scores or a general assessment of the overall neurocognitive status of the participant. The scores range from less than 70 (very low) to above 110 (above average). A higher score means higher neurocognitive function and higher capacity.
- Secondary Outcome Measures
Name Time Method Objective neuropsychological function domains of executive function, memory, processing speed, and motor speed including the CNS-Vital Signs subscale tests at 6-months. Month 6 CNS-Vital Signs Global Cognitive Index is an average score derived from the domain scores or a general assessment of the overall neurocognitive status of the participant. The scores range from less than 70 (very low) to above 110 (above average). A higher score means higher neurocognitive function and higher capacity.
Objective neuropsychological function domains of executive function, memory, processing speed, and motor speed including the CNS-Vital Signs subscale tests at 12-months. Month 12 CNS-Vital Signs Global Cognitive Index subscale is an average score derived from the domain scores or a general assessment of the overall neurocognitive status of the participant. The scores range from less than 70 (very low) to above 110 (above average). A higher score means higher neurocognitive function and higher capacity.
Modified Everyday Cognition (mECog) Months 6 and 12 Subjective participant-reported cognitive impairment including modified Everyday Cognition (mECog) scale at 3-, 6-, and 12-months.
The mECog measure uses the sum score of all of the subscales, and the items are reverse coded (i.e., 1= "Better or no change", 2="Questionable/occasionally worse", 3="Consistently a little worse", 4="Consistently much worse"), meaning that lower scores are better. Reported total scores range from 39 (Better or no change) to 156 (Consistently much worse).Exercise capacity including the 6-minute walk test (6MWT) at 6- and 12-months Months 6 and 12 Total distance in meters walked in 6 minutes
Cardiopulmonary exercise testing (CPET) Months 6 and 12 Cardiorespiratory fitness (peak VO2) using cardiopulmonary exercise testing (CPET) at 6- and 12- months. CPET is used to assess change in exercise tolerance as measured by VO2max.
Quality-of-life measures including the EuroQOL-5D-5L at 3-, 6-, and 12-months Months 3, 6, and 12 The 5-Level EuroQol-5D health questionnaire (EQ-5D-5L) is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The index value total (which is country-specific) ranges from a minimum value of -1 to a maximum value of +1. A higher EQ-5D-5L index value represents better quality of life (QoL), thus a positive change in the index value represents improved QoL.
Post-exertional malaise including the modified De Paul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM) at 6- and 12-months Months 6 and 12 The mDSQ-PEM has 10 questions (5 on severity and 5 on frequency) scored 0-4, with higher scores indicating greater post exertional malaise severity.
Effect of breathlessness on daily activities including the Modified Medical Research Council Dyspnea Scale (mMRC) at 6- and 12-months Months 6 and 12 Modified Medical Research Council Dyspnea Scale (mMRC) ranges from grade 0 to 4. 0 means no dyspnea, 1 means mild dyspnea (respiratory distress when moving quickly and climbing slightly uphill); 2 means moderate dyspnea (walking slower than peers when walking straight on, stopping to breathe); 3 means severe dyspnea (stopping to breathe after walking about 100 m or for a few minutes) and 4 means very severe dyspnea (getting out of breath while doing daily chores at home, while putting on and taking off clothes and while going to toilet).
Post COVID-19 symptom burden including the Symptom Burden Questionnaire for Long COVID (SBQ-LC) Circulation Subscale at 1-, 3-, 6-, and 12-months Months 1, 3, 6, and 12 The SBQ-LC Circulation Subscale consists of 5 questions with a score of 0-11 where higher scores indicate greater circulation-related symptom burden.
General participant-reported outcomes using the PROMIS-29 at 1-, 3-, 6-, and 12-months Months 1, 3, 6, and 12 The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 has 29 questions across seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) each scored 1-5, with higher scores indicating worse symptoms or better function, depending on the domain.
Cognitive participant-reported outcomes using the PROMIS-Cognitive Function-Short Form 8a at 1-, 3-, 6-, and 12-months Months 1, 3, 6, and 12 The Patient-Reported Outcomes Measurement Information System-Cognitive Function-Short Form 8a (PROMIS-CF-8a) has 8 questions, each scored 1-5, with higher scores indicating better cognitive function.
Mental health measures including depression, anxiety, and stress using the DASS-21 at 6- and 12-months Months 6 and 12 The Depression Anxiety Stress Scale (DASS)-21 is a set of three (depression, anxiety, stress) self reported scales. Depression: Normal 0-9, Mild 10-13, Moderate 14-20, Severe 21-27, Extremely Severe 28+. Anxiety Normal 0-7, Mild 8-9, Moderate 10-14, Severe 15-19, Extremely Severe 20+. Stress Normal 0-14, Mild 15-18, Moderate 19-25, Severe 26-33, Extremely Severe 34+.
Orthostatic intolerance using the Orthostatic Intolerance Questionnaire (OIQ) at 3-, 6-, and 12-months Months 3, 6, and 12 Each subscale is scored on a 0-10 scale, with higher scores reflecting more severe symptoms compared to few/no symptoms at lower scores. The OISA has a total possible score of 40 and the OIDAS a total possible score of 60.
Autonomic dysfunction using the COMPASS-31 at 3-, 6-, and 12-months. Months 3, 6, and 12 The Composite Autonomic Symptom Score (COMPASS)-31 has 31 questions across six health domains (orthostatic Intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor), scored 0-4 with higher scores indicating greater autonomic symptom burden.
Trial Locations
- Locations (4)
Emory University
🇺🇸Atlanta, Georgia, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Vanderbilt University Medical
🇺🇸Nashville, Tennessee, United States