Systemic InflammationPhase 2NCT05350774
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
A Phase 2 study testing IV normal saline and IV immunoglobulin in people with Systemic Inflammation and Neuroinflammation, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
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 a treatment can help with people who have recovered from COVID-19 but still have symptoms ("Long COVID"). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Systemic Inflammation, Neuroinflammation, Microvascular Thrombosis
- What is being tested?
- IV normal saline and IV immunoglobulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2023to 15 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Meets the inclusion/exclusion criteria and is enrolled in Phase A 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. Patients with severe acute COVID-19 requiring hospitalization or ICU care are excluded. Enrollment could take place 12 weeks after the diagnosis of acute COVID-19.
- Prior COVID-19 diagnosis confirmed by patient reported infection followed by confirmatory nucleocapsid antibody testing or a positive SARS-CoV-2 PCR test result from the time of infection.
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- 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.
Who cannot join
- 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.
- A condition 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.
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- Prior experimental treatment for PASC with 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.
- 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 immunoglobulins, acetaminophen, or diphenhydramine.
- A severe psychiatric condition, which based on the assessment of the study investigators, will impact the ability to complete the 12-week study course.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2 (IN-PASC)
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 a treatment can help with people who have recovered from COVID-19 but still have symptoms ("Long COVID").
Read more
Objective:
To learn if human immunoglobulin (IVIG) will help with neurological symptoms of Long COVID.
Eligibility:
Adults ages 18 and older who had COVID-19 at least 12 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 medical history and a physical exam and 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 a neurological exam.
Participants will take memory and thinking tests using a tablet. The tests will take 1 hour to complete. They will also take a smell and taste test. It will take approximately 30 minutes to complete.
Participants will lie on a table that tilts for up to 40 minutes. Their blood pressure and heart rate will be monitored. Blood will be taken through an intravenous (IV) catheter.
Participants will receive either IVIG, or saline by IV for 5 days. Then the participants will receive IVIG if they first received saline or saline if they first received IVIG by IV for another 5 days. They will not know what they receive.
Participants will have an MRI of the brain if they have not had one recently. They will receive a contrast agent by IV as part of the MRI scan.
Participants will be on the study for up to 4 months. They will have follow-up visits at the clinical center as well as fill out questionnaires at home. They may be asked to continue follow-up.
Read the detailed description
Study Description:
This study will evaluate the clinical and laboratory effects of immunoglobulin therapy in patients who recovered from acute mild-moderate COVID-19 infection but still have persistent neurologic symptoms. Despite clinical recovery from the acute infection, some individuals continue to experience ongoing symptoms, at times several months after recovery, and many of these symptoms are neurologic. Some features suggest that this is a post-infectious immune-mediated process, and anecdotally patients have responded well to immunoglobulin therapy. This study will evaluate the clinical and laboratory effects of intravenous immunoglobulin therapy compared to placebo using a cross-over trial design. It is hypothesized that immunoglobulin therapy could have positive clinical and laboratory effects on patients with persistent neurological symptoms.
Objectives:
Primary Objective: To compare the clinical efficacy of intravenous immunoglobulin therapy to placebo in ameliorating the neurological post-acute sequalae of SARS-CoV-2 infection.
Secondary objective: To determine the clinical effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV-2 infection.
Exploratory objective: To investigate the laboratory effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV-2 infection.
Endpoints:
Primary endpoint:
Proportion of participants with a clinically meaningful change in Health Utilities Index Mark 3 (HUI3) 2 weeks after intravenous immunoglobulin therapy compared with 2 weeks after placebo.
Secondary endpoints:
- Change in functional / patient-reported scales:
- WHO post COVID-19 functional scale
- Post-COVID-19 Functional Status (PCFS) scale (0-4).
- COVID-19 Yorkshire Rehabilitation Scale
- PROMIS Global Health score
- PROMIS Depression score
- PROMIS anxiety score
- Change in clinical scales:
- Montreal Cognitive Assessment (MoCA)
- Brief tablet-based Neuropsychiatric evaluation
- Karnofsky Performance Status (KPS)
Exploratory endpoints:
- Autonomic testing - Change in the number and character of test results indicating autonomic nervous system dysfunctions as evidenced by abnormal physiological responses to the Valsalva maneuver or head-up tilting.
- Change in immunological markers:
- Cytokine levels
- Cell markers per flow cytometry
- SCENTinel, Olfactory testing, Monell
- Being tested
- IV normal saline, IV immunoglobulin
- Keywords
- Long Haul Covid, COVID-19, Long Covid
- Medical subject headings
- Neuroinflammatory Diseases, Post-Acute COVID-19 Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV normal salineDrug
IV normal saline 250ml for 5 days
IV immunoglobulinDrug
IVIg - IV immunoglobulin 0.4g/kg/day for 5 days
| Study group | Role | What they receive |
|---|---|---|
| IVIg arm | Experimental | IVIg arm IV immunoglobulin 0.4g/kg/day for 5 days Receives: Drug: IV immunoglobulin |
| Placebo arm | Placebo comparator | equivalent volume of Normal Saline for 5 days Receives: Drug: IV normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of intravenous immunoglobulin therapy
Comparison of proportion of participants with a clinically meaningful change in Health Utilities Index Mark 3 (HUI3) after receiving either IVIg or placebo at Week 2.
Measured: 2 weeks
Secondary outcomes (1)
Investigate laboratory effects
Comparison of change in functional / patient-reported scales at 2 weeks after receiving each study intervention:a.<TAB>WHO post-COVID functional scale b.<TAB>PCFSc.<TAB>COVID-19 Yorkshire Rehabilitation Scaled.<TAB>PROMIS GHe.<TAB>PROMIS Depression f.<TAB>PROMIS Anxiety Comparison of change in clinical scales 2 weeks after receiving each study intervention:g.<TAB>Montreal Cognitive Assessment (MoCA)h.<TAB>Brief tablet-based Neuropsychiatric evaluation i.<TAB>Karnofsky Performance Status (KPS)
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2022
- Study start10 Jul 2023
- Primary completion15 Dec 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic InflammationStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Avindra Nath, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05350774
- Sponsor's protocol ID
- 10000711
- Other IDs
- 000711-N
- Status last verified
- 30 Oct 2026
- First submitted
- 20 Apr 2022
- Last updated
- 3 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2 (IN-PASC)
- ClinicalTrials.gov ID
- NCT05350774
- Acronym / sponsor ID
- 10000711
- Keywords
- Long Haul Covid, COVID-19, Long Covid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 10 Jul 2023 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 28 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 a treatment can help with people who have recovered from COVID-19 but still have symptoms ("Long COVID").
Objective:
To learn if human immunoglobulin (IVIG) will help with neurological symptoms of Long COVID.
Eligibility:
Adults ages 18 and older who had COVID-19 at least 12 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 medical history and a physical exam and 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 a neurological exam.
Participants will take memory and thinking tests using a tablet. The tests will take 1 hour to complete. They will also take a smell and taste test. It will take approximately 30 minutes to complete.
Participants will lie on a table that tilts for up to 40 minutes. Their blood pressure and heart rate will be monitored. Blood will be taken through an intravenous (IV) catheter.
Participants will receive either IVIG, or saline by IV for 5 days. Then the participants will receive IVIG if they first received saline or saline if they first received IVIG by IV for another 5 days. They will not know what they receive.
Participants will have an MRI of the brain if they have not had one recently. They will receive a contrast agent by IV as part of the MRI scan.
Participants will be on the study for up to 4 months. They will have follow-up visits at the clinical center as well as fill out questionnaires at home. They may be asked to continue follow-up.
Detailed description
Study Description:
This study will evaluate the clinical and laboratory effects of immunoglobulin therapy in patients who recovered from acute mild-moderate COVID-19 infection but still have persistent neurologic symptoms. Despite clinical recovery from the acute infection, some individuals continue to experience ongoing symptoms, at times several months after recovery, and many of these symptoms are neurologic. Some features suggest that this is a post-infectious immune-mediated process, and anecdotally patients have responded well to immunoglobulin therapy. This study will evaluate the clinical and laboratory effects of intravenous immunoglobulin therapy compared to placebo using a cross-over trial design. It is hypothesized that immunoglobulin therapy could have positive clinical and laboratory effects on patients with persistent neurological symptoms.
Objectives:
Primary Objective: To compare the clinical efficacy of intravenous immunoglobulin therapy to placebo in ameliorating the neurological post-acute sequalae of SARS-CoV-2 infection.
Secondary objective: To determine the clinical effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV-2 infection.
Exploratory objective: To investigate the laboratory effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV-2 infection.
Endpoints:
Primary endpoint:
Proportion of participants with a clinically meaningful change in Health Utilities Index Mark 3 (HUI3) 2 weeks after intravenous immunoglobulin therapy compared with 2 weeks after placebo.
Secondary endpoints:
- Change in functional / patient-reported scales:
- WHO post COVID-19 functional scale
- Post-COVID-19 Functional Status (PCFS) scale (0-4).
- COVID-19 Yorkshire Rehabilitation Scale
- PROMIS Global Health score
- PROMIS Depression score
- PROMIS anxiety score
- Change in clinical scales:
- Montreal Cognitive Assessment (MoCA)
- Brief tablet-based Neuropsychiatric evaluation
- Karnofsky Performance Status (KPS)
Exploratory endpoints:
- Autonomic testing - Change in the number and character of test results indicating autonomic nervous system dysfunctions as evidenced by abnormal physiological responses to the Valsalva maneuver or head-up tilting.
- Change in immunological markers:
- Cytokine levels
- Cell markers per flow cytometry
- SCENTinel, Olfactory testing, Monell
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IVIg arm | Experimental | Drug: IV immunoglobulinIVIg arm IV immunoglobulin 0.4g/kg/day for 5 days |
| Placebo arm | Placebo comparator | Drug: IV normal salineequivalent volume of Normal Saline for 5 days |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- Meets the inclusion/exclusion criteria and is enrolled in Phase A 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. Patients with severe acute COVID-19 requiring hospitalization or ICU care are excluded. Enrollment could take place 12 weeks after the diagnosis of acute COVID-19.
Key exclusion criteria (19 listed)
- 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.
- A condition 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV normal salineIV normal saline 250ml for 5 days | Drug | Placebo arm |
| IV immunoglobulinIVIg - IV immunoglobulin 0.4g/kg/day for 5 days | Drug | IVIg arm |
Primary outcome
Effects of intravenous immunoglobulin therapy
Time frame: 2 weeks
Comparison of proportion of participants with a clinically meaningful change in Health Utilities Index Mark 3 (HUI3) after receiving either IVIg or placebo at Week 2.
1 secondary outcome
Investigate laboratory effects
Time frame: 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Avindra Nath, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV normal saline and IV immunoglobulin in people with Systemic Inflammation and Neuroinflammation, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of intravenous immunoglobulin therapy (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.