RECRUITING

Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID

Conditions

Long COVID Sars-CoV-2 Infection Coronavirus Infections COVID-19 Long COVID Drug Treatment

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID (REVERSE-LC)

Quick Facts

Study Start:2024-10-11

Study Completion:2027-07-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06631287

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Evidence of personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and was willing and able to consent to participation. 2. Age ≥18 years old. 3. Documented SARS-CoV-2 infection 6 or more months prior using an Antigen or NAAT. 4. Clinical evidence of Long COVID, as confirmed by the investigator's assessment: 1. Evidence of personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and was willing and able to consent to participation. 2. Age ≥18 years old. 3. Clinical diagnosis of COVID infection 6 or more months prior 4. Clinical evidence of Long COVID, as confirmed by the clinician's assessment:	1. Pre-existing cognitive impairment not exacerbated by COVID-19, including but not limited to syphilis, as determined by study clinicians (MD, DO, NP, PA, RN, or equivalent), which may include a review of participant's history and medical records. 2. Severe cognitive, physical, or psychological disability preventing participation in the study, as determined by the investigator. 3. Moderate or High risk of suicidality, as determined by the modified Columbia Suicide Severity Rating Scale (mC-SSRS). 4. History of a major adverse cardiovascular event (MACE) within the 3 months prior to enrollment. 5. Current use of baricitinib or other disease-modifying antirheumatic drug (DMARDs) 6. Known prior allergic reactions to components of the baricitinib. 7. Previously randomized in this study or in the last 30 days have been in another study investigating baricitinib. 8. Current probenecid use. 9. Positive SARS-CoV-2 NAAT or rapid Antigen test in the 14 days prior to screening. 10. Currently pregnant or breastfeeding or planning to become pregnant or breastfeed during the course of the study. 11. Venous thromboembolism in the past 6 months prior to screening or felt to be at increased risk of thrombosis by the investigator. 12. Malignancy or lymphoproliferative disorder not in remission for at least 5 years. Local non-melanoma skin cancers that are definitively managed are not exclusionary. 13. Previous admission to an ICU for treatment of acute COVID-19 infection. 14. Estimated glomerular filtration rate of \< 30 mL/min/1.73m2, as calculated using the CKD-EPI 2021 equation. 15. Absolute Neutrophil Count (ANC) \<1000 cells/mm3, confirmed on repeat testing. 16. Absolute Leukocyte Count (ALC) \<100 cells/mm3. 17. Evidence of severe liver disease at the time of screening, defined as Bilirubin \> 1.5 X ULN or AST or ALT \> 2x ULN. 18. Alkaline Phosphatase (ALP) ≥ 3x ULN. 19. Creatine Phosphokinase (CPK) ≥ 3x ULN. 20. Hemoglobin (HgB) \< 8 g/dL, confirmed on repeat testing. 21. Platelets \<100,000 cells/mm3, confirmed on repeat testing. 22. Platelets \>500,000 cells/mm3, confirmed on repeat testing. 23. Total fasting cholesterol ≥ 280 mg/dL, confirmed on repeat testing. 24. Fasting LDL ≥ 180 mg/dL, confirmed on repeat testing. 25. Positive Hepatitis B surface antigen or Hepatitis B core antibody. Note: Individuals with a positive Hepatitis B core antibody will be excluded even in the presence of a positive Hepatitis B surface antibody due to the risk of reactivation. 26. Positive for Hepatitis C at the time of Screening. Note: treated or cleared Hepatitis C is not exclusionary. 27. Symptomatic herpes zoster infection (i.e., visible herpetic skin lesions of Zoster) within 3 months prior to study screening, or any history of disseminated/complicated herpes zoster or herpes simplex infection (e.g., VZV encephalitis). 28. History of untreated latent tuberculosis infection (diagnosed with QuantiFERON-TB Gold Plus testing) or active tuberculosis whether treated or untreated. Note: those with a positive PPD who have a history of BCG vaccine and a negative QuantiFERON-TB Gold Plus test will remain eligible). 29. History of current or recent (\< 30 days from screening) sepsis or clinically significant viral, bacterial, fungal, or parasitic infection, according to the determination of the investigator. 30. Participants with HIV will be excluded if they have been on ART \<1 year, have a CD4+ T cell count \<500 cells/ml (confirmed on repeat), or have two consecutive HIV plasma RNA viral load \> 48 copies/mL within 1 year of study screening, including requiring the most recent within 3 months of screening. Blips (VL \> 48 copies/mL but \< 200 copies/mL) are permitted if preceded and followed by values below the assay limit of quantification. 31. Immunocompromised as defined by NIH COVID-19 guidelines (see Appendix) and, in the opinion of the investigator, at an unacceptable risk for participating in the study. 32. Treatment with another investigational drug or device as part of an interventional study within 30 days of study screening. 33. In the opinion of the investigator, unable to reliably follow-up for the duration of the study and/or are unable to follow study restrictions/procedures. 34. Persons of childbearing potential under age 55 who are unwilling or unable to abstain from sex or to use at least one acceptable method of contraception from the time of screening though at least 28 days after the end of the study intervention period. Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), other contraceptives, oral contraceptive pills, and surgical sterilization. Participants unwilling to be counseled about risks related to pregnancy or breastfeeding. 35. Participants actively breastfeeding, who are unwilling to stop breastfeeding for the duration of the trial. 36. Currently incarcerated

Inclusion Criteria

Exclusion Criteria

1. Evidence of personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and was willing and able to consent to participation.
2. Age ≥18 years old.
3. Documented SARS-CoV-2 infection 6 or more months prior using an Antigen or NAAT.
4. Clinical evidence of Long COVID, as confirmed by the investigator's assessment:
1. Evidence of personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and was willing and able to consent to participation.
2. Age ≥18 years old.
3. Clinical diagnosis of COVID infection 6 or more months prior
4. Clinical evidence of Long COVID, as confirmed by the clinician's assessment:

1. Pre-existing cognitive impairment not exacerbated by COVID-19, including but not limited to syphilis, as determined by study clinicians (MD, DO, NP, PA, RN, or equivalent), which may include a review of participant's history and medical records.
2. Severe cognitive, physical, or psychological disability preventing participation in the study, as determined by the investigator.
3. Moderate or High risk of suicidality, as determined by the modified Columbia Suicide Severity Rating Scale (mC-SSRS).
4. History of a major adverse cardiovascular event (MACE) within the 3 months prior to enrollment.
5. Current use of baricitinib or other disease-modifying antirheumatic drug (DMARDs)
6. Known prior allergic reactions to components of the baricitinib.
7. Previously randomized in this study or in the last 30 days have been in another study investigating baricitinib.
8. Current probenecid use.
9. Positive SARS-CoV-2 NAAT or rapid Antigen test in the 14 days prior to screening.
10. Currently pregnant or breastfeeding or planning to become pregnant or breastfeed during the course of the study.
11. Venous thromboembolism in the past 6 months prior to screening or felt to be at increased risk of thrombosis by the investigator.
12. Malignancy or lymphoproliferative disorder not in remission for at least 5 years. Local non-melanoma skin cancers that are definitively managed are not exclusionary.
13. Previous admission to an ICU for treatment of acute COVID-19 infection.
14. Estimated glomerular filtration rate of \< 30 mL/min/1.73m2, as calculated using the CKD-EPI 2021 equation.
15. Absolute Neutrophil Count (ANC) \<1000 cells/mm3, confirmed on repeat testing.
16. Absolute Leukocyte Count (ALC) \<100 cells/mm3.
17. Evidence of severe liver disease at the time of screening, defined as Bilirubin \> 1.5 X ULN or AST or ALT \> 2x ULN.
18. Alkaline Phosphatase (ALP) ≥ 3x ULN.
19. Creatine Phosphokinase (CPK) ≥ 3x ULN.
20. Hemoglobin (HgB) \< 8 g/dL, confirmed on repeat testing.
21. Platelets \<100,000 cells/mm3, confirmed on repeat testing.
22. Platelets \>500,000 cells/mm3, confirmed on repeat testing.
23. Total fasting cholesterol ≥ 280 mg/dL, confirmed on repeat testing.
24. Fasting LDL ≥ 180 mg/dL, confirmed on repeat testing.
25. Positive Hepatitis B surface antigen or Hepatitis B core antibody. Note: Individuals with a positive Hepatitis B core antibody will be excluded even in the presence of a positive Hepatitis B surface antibody due to the risk of reactivation.
26. Positive for Hepatitis C at the time of Screening. Note: treated or cleared Hepatitis C is not exclusionary.
27. Symptomatic herpes zoster infection (i.e., visible herpetic skin lesions of Zoster) within 3 months prior to study screening, or any history of disseminated/complicated herpes zoster or herpes simplex infection (e.g., VZV encephalitis).
28. History of untreated latent tuberculosis infection (diagnosed with QuantiFERON-TB Gold Plus testing) or active tuberculosis whether treated or untreated. Note: those with a positive PPD who have a history of BCG vaccine and a negative QuantiFERON-TB Gold Plus test will remain eligible).
29. History of current or recent (\< 30 days from screening) sepsis or clinically significant viral, bacterial, fungal, or parasitic infection, according to the determination of the investigator.
30. Participants with HIV will be excluded if they have been on ART \<1 year, have a CD4+ T cell count \<500 cells/ml (confirmed on repeat), or have two consecutive HIV plasma RNA viral load \> 48 copies/mL within 1 year of study screening, including requiring the most recent within 3 months of screening. Blips (VL \> 48 copies/mL but \< 200 copies/mL) are permitted if preceded and followed by values below the assay limit of quantification.
31. Immunocompromised as defined by NIH COVID-19 guidelines (see Appendix) and, in the opinion of the investigator, at an unacceptable risk for participating in the study.
32. Treatment with another investigational drug or device as part of an interventional study within 30 days of study screening.
33. In the opinion of the investigator, unable to reliably follow-up for the duration of the study and/or are unable to follow study restrictions/procedures.
34. Persons of childbearing potential under age 55 who are unwilling or unable to abstain from sex or to use at least one acceptable method of contraception from the time of screening though at least 28 days after the end of the study intervention period. Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), other contraceptives, oral contraceptive pills, and surgical sterilization. Participants unwilling to be counseled about risks related to pregnancy or breastfeeding.
35. Participants actively breastfeeding, who are unwilling to stop breastfeeding for the duration of the trial.
36. Currently incarcerated

Contacts and Locations

Study Contact

Amy E. Bazzoni, BA

CONTACT

615-343-8010

vccrvlcstudy@vumc.org

Wes Ely, M.D.

CONTACT

Principal Investigator

Wes Ely, M.D.

PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Study Locations (Sites)

Vanderbilt University Medical

Nashville, Tennessee, 37203

United States

Collaborators and Investigators

Sponsor: Wes Ely

Wes Ely, M.D., PRINCIPAL_INVESTIGATOR, Vanderbilt University Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-11

Study Completion Date2027-07-01

Study Record Updates

Study Start Date2024-10-11

Study Completion Date2027-07-01

Terms related to this study

Keywords Provided by Researchers

COVID-19
Long COVID Drug Treatment
Long COVID

Additional Relevant MeSH Terms

Long COVID
Sars-CoV-2 Infection
Coronavirus Infections
COVID-19