Post-acute Sequelae of COVID-19, Long COVID
Conditions
Brief summary
The purpose of this research study is to test if the combination of three drugs, valacyclovir, celecoxib, and Paxlovid will decrease the symptoms of Long COVID in adults compared to a placebo (this does not contain the medications).
Detailed description
This is an off-label, randomized, double-blind, active placebo-controlled, two-arm clinical trial of a combination of celecoxib, valacyclovir, and Paxlovid in adults with Long COVID. This study aims to evaluate the safety and efficacy of the combination of celecoxib, valacyclovir, and Paxlovid in adults with Long COVID (LC). Safety will be primarily measured through blood and urine measures. Efficacy will be evaluated by measuring patient-reported outcomes.
Interventions
DRUGValacyclovir
one to two 750mg capsules taken orally in the morning and evening
DRUGCelecoxib
200mg capsules taken orally in the morning and evening
DRUGPaxlovid
one (100mg ritonavir tablet and two 150mg nirmatrelvir tablets) taken orally in the morning and evening
DRUGPlacebo
matching placebo capsules and tablets taken orally in the morning and evening
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years of age at the time of study entry * Diagnosed with Long COVID * Individuals of child-bearing potential must have a negative serum pregnancy test at screening and agree to on-site urine pregnancy testing at all subsequent study visits * A urine drug screen performed at the Screening Visit must be negative for drugs of abuse such as methamphetamine, cocaine, phencyclidine (PCP), and non-disclosed amphetamines and opioids/opiates. * Those with mild to moderate depression should be clinically stable for three months, without risk of suicidal ideation or behavior.
Exclusion criteria
* Breastfeeding, pregnant, or planning to become pregnant during the next six months. * In the opinion of the Investigator, any clinically significant, uncontrolled, or unstable medical or surgical condition that could affect the individual's ability to participate in the study or potentially compromise their well-being while enrolled in the study. * In the opinion of the Investigator or based on results of the HADS, evidence of a clinically significant psychiatric disorder, e.g., severe, unstable or poorly controlled depression, anxiety or obsessive-compulsive disorder; moderate or severe alcohol use disorder; substance use disorder other than mild cannabis use disorder; or any history of bipolar disorder, schizophrenia, schizoaffective disorder or other psychotic disorder. * Currently meeting criteria for ME/CFS at the pre-screening or screening visit, or a prior confirmed diagnosis of ME/CFS within the last 5 years. This may be determined as part of the initial screening call or visit. * Any anticipated need for surgery that in the opinion of the Principal Investigator or Sub-I might confound results or interfere with the participant's ability to comply with the protocol. * Symptomatic and/or otherwise clinically significant cardiac disease * Acute non-COVID systemic infection (e.g., HIV, hepatitis) or other active viral or bacterial infection during the screening/washout period or at the Baseline visit. * Currently receiving chronic systemic corticosteroids (\>5 mg prednisone daily, or equivalent) * Routine treatment with warfarin, heparin, lithium, digoxin, amiodarone, isoniazid, phenytoin, fluconazole, methotrexate, probenecid, or raloxifene. Participants on these medications should not be screened. * Uncontrolled sleep apnea. * Use of chronic nucleoside analog antiviral suppression therapy within one month of the Screening Visit or requiring on average more than one acute treatment course every two months. * Current use of celecoxib either alone or in combination with valacyclovir or famciclovir * In the opinion of the Investigator, evidence of current drug or alcohol abuse or dependency, or history of abuse or dependence during the preceding 12 months. * The participant has undergone a malabsorptive weight loss procedure (e.g., Roux-en-Y or other bypass procedure). * Severe IBS-C or colonic inertia as evidenced by seven or more days between bowel movements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EQ-5D-5L Visual Analogue Scale (VAS) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The EQ VAS records the patient's self-rated health on a visual analogue scale where the endpoints are labelled 'The best health you can imagine' (100) and 'The worst health you can imagine' (0), with higher scores indicating better health state. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The EuroQol Five-Dimensional Health Questionnaire (EQ-5D-5L) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The EQ-5D-5L is a validated, standardized, generic instrument that is a preference-based health- related quality of life questionnaire. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Full scale from 5 to 25, with higher score indicating poorer health outcomes. |
| Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The PROMIS-29 v2.0 profile assesses pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) using four items per domain. The values of all item responses are averaged to generate subscores for each dimension. From these subscores, a global physical health score and a global mental health score are generated. The scores are translated into T-scores according to a reference population with a mean of 50 and a standard deviation of 10. |
| General Symptom Questionnaire (GSQ-30) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The General Symptom Questionnaire-30 (GSQ-30) is a valid and reliable instrument to assess symptom burden among patients with acute and post-treatment. The GSQ-30 total score ranges from 0 to 120, with higher scores indicating a greater symptom burden. |
| Patient Health Questionnaire (PHQ-9) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The PHQ-9 is a series of questions assessing presence and severity of depression symptoms. It evaluates each of the DSM-IV depression criteria and scores the responses from 0 ("Not at all") to 3 ("Nearly every day"). PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Full scale from 0-27, with higher score indicating more severe symptoms. |
| Generalized Anxiety Disorder (GAD-7) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The GAD-7 is a 7-item scale developed and validated to identify generalized anxiety disorder and its severity. It assesses the frequency of 7 anxiety symptoms and scores the responses from 0 ("Not at all") to 3 ("Nearly every day"). Total scores of 5, 10, and 15 correspond to mild, moderate, and severe generalized anxiety disorder, respectively. Full scale from 0-21, with higher score indicating more symptoms. |
| COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | A suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions that anyone can ask. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation). Higher score represents poorer health outcomes. |
| Neuro-QoL™ v2.0 Cognitive Function-Short Form | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The Neuro-QoL Cognitive Function v2.0 short form assesses perceived difficulties in cognitive abilities, including memory, attention, decision making, planning, organizing, calculating, remembering, and learning. The short form consists of 8 questions assessed on a 5-point Likert scale, resulting in a raw score range of 8 to 40. A raw score is then converted to a T-score using conversion tables. Scores 0.5 - 1.0 SD worse than the mean (T-score 40-45) = mild symptoms/impairment. Scores 1.0 - 2.0 SD worse than the mean (T-score 30-40) = moderate symptoms/impairment. Scores 2.0 SD or more worse than the mean (T-score below 30) = severe symptoms/impairment. |
| Single-item Sleep Quality Scale (SQS) | Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, Week 20 | The SQS is a visual analog scale that instructs respondents to rate their overall quality of sleep over a 7-day recall period from 0 to 10. Scores of 0, 1, 4, 7, and 10 correspond to terrible, poor, fair, good, and excellent, respectively. Higher scores indicate better sleep quality. |
Countries
United States
Contacts
CONTACTDavid Putrino, PhD
PRINCIPAL_INVESTIGATORDavid Putrino, PhD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed