Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05350774 |
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Recruitment Status :
Enrolling by invitation
First Posted : April 28, 2022
Last Update Posted : February 3, 2023
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Background:
COVID-19 can cause problems in different parts of the body. For most people, it causes fevers or trouble breathing. Some people might not recover all the way. Researchers want to see if 2 treatments can help with people who have recovered from COVID-19 but still have symptoms ( Long-Haul COVID ).
Objective:
To learn if methylprednisolone (steroid) and human immunoglobulin (IVIG) will help with symptoms of Long-Haul COVID.
Eligibility:
Adults ages 18 and older who had COVID-19 at least 6 weeks ago and have ongoing neurologic symptoms, such as dizziness, trouble walking, or problems with strength.
Design:
Participants will be screened with a medical record review.
Participants will have a physical exam and chest x-ray. They will complete questionnaires about their health and quality of life. They will have a spinal tap. They will give blood samples. They will discuss their symptoms with a neurologist and have an exam.
Participants will take memory and thinking tests using pen and paper. The tests will take 10-15 minutes to complete. They will also take a smell test with scratch-and-sniff books. It will take 5-10 minutes to complete.
Participants will lie on a table that tilts. Their blood pressure and heart rate will be monitored. Blood will be taken through an intravenous (IV) catheter.
Participants will receive either the steroid, IVIG, or saline by IV for 5 days. They will not know which treatment they get.
Participants may have an optional MRI of the brain and spine. They will receive a contrast agent by IV.
Participants will be on the study for up to 3 months. They may be asked to continue follow-up.
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Systemic Inflammation Neuroinflammation Microvascular Thrombosis | Drug: IV immunoglobulin Drug: IV normal saline Drug: IV methylprednisolone | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2 (IN-PASC) |
| Estimated Study Start Date : | February 8, 2023 |
| Estimated Primary Completion Date : | April 6, 2023 |
| Estimated Study Completion Date : | April 6, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: IVIg arm
IVIg arm IV immunoglobulin 0.4g/kg/day for 5 days
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Drug: IV immunoglobulin
IVIg - IV immunoglobulin 0.4g/kg/day for 5 days |
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Placebo Comparator: Placebo arm
IV normal saline 250ml for 5 days
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Drug: IV normal saline
IV normal saline 250ml for 5 days |
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Experimental: Steroid arm
Steroid arm IV methylprednisolone 1g/day for 5 days
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Drug: IV methylprednisolone
Steroid - IV methylprednisolone 1g/day for 5 days |
- Effects of immunotherapies in patients [ Time Frame: 4 weeks after treatment ]The primary outcome measure is the proportion of participants with a clinically meaningful improvement in Health Utilities Index Mark 3 (HUI3) 4 weeks after study intervention.
- Investigate laboratory effects [ Time Frame: 4 weeks after treatment ]To investigate laboratory effects of immunotherapies in patients with neurological post-acute sequelae of SARS-CoV-2 infection.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged at least 18 and older.
- Enrolled in the screening phase of Protocol 000089 'Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health.'
- Previously diagnosed with mild-moderate COVID-19 (WHO Clinical Progression Scale between 2-5). Enrollment could take place between 12 weeks and 18 months after the diagnosis of acute COVID-19.
- Prior COVID-19 diagnosis confirmed by patient reported positive antigen test for SARS-CoV-2 followed by confirmatory nucleocapsid antibody testing or a positive SARS-CoV-2 PCR test result from the time of infection.
- Exhibiting persistent neurologic symptoms evidenced by a self-reported illness narrative of the development of persistent PASC symptoms after recovering from a SARS-CoV-2 infection. These include symptoms such as fatigue, cognitive difficulties, orthostatic intolerance, and any ongoing issues with gait instability, vision, speech, swallowing, sensation or strength.
- Non-negligible PASC symptom severity, as determined using PCFS (minimal score of 2).
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Prior completion of a clinical brain MRI after the diagnosis of COVID-19, or willingness to complete a brain MRI.
- Meets current Clinical Center HES policy for discontinuing isolation and quarantine for COVID-19.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- For participants who have not completed a brain MRI since onset of symptoms: inability to complete brain MRI with gadolinium including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR <45 mmol/L, pregnancy or lactation, or claustrophobia that is unable to be adequately treated with a low dose oral
benzodiazepine.
- Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets < 50,000/uL, PT or PTT >1.5 x ULN for the NIH Clinical Center, or otherwise inability to complete the procedure.
- Contraindication to autonomic testing, including refractory ventricular arrhythmias or symptomatic coronary artery disease.
- A condition prior to the diagnosis of COVID-19 infection that would significantly confound interpretation of the clinical and research tests as determined by the study investigators. This could include: traumatic brain injury, substance use disorder, active malignancy, systemic immunologic disorders, current or previous long-term immune suppressive therapy.
- Received a SARS-CoV-2 vaccine dose within less than 4 weeks of enrollment or is planning for any additional vaccines during the course of the study.
- Prior experimental treatment for PASC with IV steroids or immunoglobulins.
- Current medications include oral steroids or other immunosuppressive medications.
- Active participation in a clinical protocol which includes any intervention that may affect the results of the current study.
- Diabetes mellitus treated with medications or HbA1c >6.5.
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Contraindication of intravenous immunoglobulins, including:
- Renal insufficiency (eGFR<45mmol/L)
- IgA deficiency
- History of ischemic heart disease
- Peripheral vascular disease
- Cerebrovascular disease
- Previously diagnosed hypercoagulability syndrome including antiphospholipid antibody syndrome, Protein C/S deficiency, Factor V Leiden, Antithrombin deficiency, MTHFR homozygosity
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3.0 times the upper limit of normal.precluding the use of acetaminophen.
- Previously documented anaphylaxis or severe systemic reaction to steroids, immunoglobulins, acetaminophen, or diphenhydramine.
- Positive QuantiFERON-TB Gold test.
- A severe psychiatric condition prior to the diagnosis of COVID-19, which based on the assessment of the study investigators, will significantly increase the risk of psychiatric side effects from IV steroids.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05350774
| United States, Maryland | |
| National Institutes of Health Clinical Center | |
| Bethesda, Maryland, United States, 20892 | |
| Principal Investigator: | Avindra Nath, M.D. | National Institute of Neurological Disorders and Stroke (NINDS) |
| Responsible Party: | National Institute of Neurological Disorders and Stroke (NINDS) |
| ClinicalTrials.gov Identifier: | NCT05350774 |
| Other Study ID Numbers: |
10000711 000711-N |
| First Posted: | April 28, 2022 Key Record Dates |
| Last Update Posted: | February 3, 2023 |
| Last Verified: | January 18, 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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COVID-19 Long Haul Covid |
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Thrombosis Inflammation Pathologic Processes Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Methylprednisolone Immunoglobulins Immunoglobulins, Intravenous gamma-Globulins Rho(D) Immune Globulin Anti-Inflammatory Agents |
Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Neuroprotective Agents Protective Agents Immunologic Factors |