Immunotherapy for Long-Haul COVID

Overseen By Amanda M Wiebold

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Must not be taking: Oral steroids, Immunosuppressives

Disqualifiers: Traumatic brain injury, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 11

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an immunotherapy treatment called IVIG (intravenous immunoglobulin) can aid individuals with ongoing neurological problems after recovering from COVID-19, often referred to as Long COVID. The focus is on symptoms such as dizziness, trouble walking, or muscle weakness. The study targets those who had COVID-19 at least 12 weeks ago and still experience these symptoms. Participants will receive either the IVIG treatment or a placebo (a harmless substance) for comparison, without knowing which one they receive. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial excludes participants who are currently taking oral steroids or other immunosuppressive medications, so you may need to stop these medications to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that intravenous immunoglobulin (IVIG) has been safely used for various health issues. It effectively treats autoimmune neuropathies, where the immune system attacks the nerves. Studies suggest that IVIG is generally well-tolerated, even during pregnancy, and has shown promising results in severe COVID-19 cases.

In severe COVID-19 cases, patients who received high doses of IVIG had a lower risk of death compared to those who did not. This suggests that IVIG might be safe and helpful in serious situations. However, researchers are still studying its long-term safety for treating Long COVID.

While the safety outlook is encouraging, this treatment is currently in Phase 2 trials for Long COVID. It has passed initial safety tests but is still being studied to confirm its effectiveness and safety in a larger group. Participants are encouraged to ask questions and discuss any concerns with the research team before joining the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Long COVID?

Unlike the standard treatments for long-haul COVID, which often focus on managing symptoms with medications like corticosteroids or antivirals, IV immunoglobulin (IVIg) offers a different approach. IVIg is derived from human plasma and works by modulating the immune system, potentially reducing inflammation and helping the body better regulate its immune response. Researchers are excited about this treatment because it could provide relief within just five days, offering a quicker alternative to existing therapies that can take weeks or months to show significant improvement.

What evidence suggests that IVIG might be an effective treatment for Long COVID?

Research has shown that intravenous immunoglobulin (IVIG) may help treat various conditions affecting the nervous and immune systems. One study found that high doses of IVIG over a long period helped people with Long COVID. In this trial, participants in the IVIG arm will receive IV immunoglobulin to evaluate its effectiveness for Long COVID. Patients with autoimmune nerve disorders have also benefited from IVIG, and it has shown promise for severe COVID-19 cases. Specifically, another study suggested that severe COVID-19 patients who received high-dose IVIG had a lower risk of death. These findings suggest that IVIG could help with neurological symptoms in Long COVID patients. ^{1 2 4 5 6}

Who Is on the Research Team?

Avindra Nath, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

Adults over 18 who had mild to moderate COVID-19 at least 12 weeks ago and are now experiencing persistent neurological symptoms like dizziness, cognitive issues, or walking difficulties. They must be willing to follow the study procedures for up to 4 months and have a brain MRI if they haven't already. People with severe psychiatric conditions, recent vaccines, certain medical treatments or conditions that could affect results are excluded.

Inclusion Criteria

Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health

I have had or am willing to have a brain MRI after being diagnosed with COVID-19.

I had COVID-19 but it was not severe enough to need hospital or ICU care.

Exclusion Criteria

You cannot have a brain MRI with a contrast agent if you have metal in your body, kidney function below a certain level, are pregnant or breastfeeding, or have severe claustrophobia.

You have certain medical conditions like kidney problems, heart disease, blood clotting disorders, severe allergies, or psychiatric conditions that make it unsafe for you to receive intravenous immunoglobulins.

I cannot have a spinal tap due to certain health issues or medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either IVIG or saline by IV for 5 days, followed by a crossover to the other treatment for another 5 days

2 weeks

Daily visits for 10 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including follow-up visits and questionnaires

up to 4 months

Follow-up visits at the clinical center and questionnaires at home

What Are the Treatments Tested in This Trial?

Interventions

• IV immunoglobulin

Trial Overview The trial is testing whether IV immunoglobulin (IVIG), compared to saline solution (a placebo), can improve long-term neurological symptoms after COVID-19 recovery. Participants will receive both treatments in different periods without knowing which one they're getting first.

How Is the Trial Designed?

Group I: IVIg arm Experimental Treatment 1 Intervention

IVIg arm IV immunoglobulin 0.4g/kg/day for 5 days

Group II: Placebo arm Placebo Group 1 Intervention

equivalent volume of Normal Saline for 5 days

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a case series of five patients with COVID-19-related encephalopathy, intravenous immunoglobulin (IVIg) therapy led to complete recovery of neurological symptoms, with initial improvements seen within an average of 3.4 days after treatment began.

IVIg was administered safely, with no adverse events reported, suggesting its potential as an effective treatment due to its anti-inflammatory and anti-cytokine properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin therapy in COVID-19-related encephalopathy. Muccioli, L., Pensato, U., Bernabè, G., et al.[2021]

In a study of 305 intravenous immunoglobulin G (IVIG) infusions given to 111 pediatric patients, only 3.9% of infusions resulted in adverse reactions, indicating a low incidence of side effects in this population.

The most severe adverse reactions included two cases of aseptic meningitis and one case of seizures, all of which resolved completely, suggesting that while IVIG is generally safe, monitoring for rare severe reactions is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. Yori, S., Belleri, F., Testard, J., et al.[2021]

The development of intravenous anti-COVID-19 hyperimmune immunoglobulin resulted in a product with a high concentration of neutralizing antibodies (9.4 times concentrated) and a protein content of 98.1 mg/ml, primarily consisting of IgG (97.6%).

Safety studies in animal models showed no toxicity or allergic reactions, and the immunoglobulin effectively protected immunosuppressed hamsters from SARS-CoV-2, paving the way for future clinical trials in healthy adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterization of anti-SARS-CoV-2 intravenous immunoglobulin from COVID-19 convalescent plasma. Razumikhin, M., Smolyanova, T., Nikolaeva, A., et al.[2022]

Intravenous immunoglobulin (IVIg) therapy may be beneficial for certain COVID-19 patients, particularly those in the late phase of the disease or those experiencing sepsis due to bacterial superinfection, as identified by a panel of experts.

The panel found the rationale for using IVIg in the early phase of COVID-19 to be uncertain, highlighting the need for ongoing trials to determine the most effective use of this therapy in managing severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for Polyclonal Intravenous Immunoglobulin Adjunctive Therapy in COVID-19 Patients: Report of a Structured Multidisciplinary Consensus. Coloretti, I., Berlot, G., Busani, S., et al.[2021]

Intravenous immunoglobulins (IVIgs) are generally considered safe for treating neuroimmunologic and autoimmune diseases, with severe complications being rare and often linked to preexisting risk factors.

While mild and self-limited side effects can occur, careful screening of patients and monitoring of laboratory parameters can help minimize the risks associated with IVIg therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of high-dose intravenous immunoglobulins. Stangel, M., Hartung, HP., Marx, P., et al.[2019]

In a study of 850 severe COVID-19 patients, IVIG treatment did not significantly reduce 28-day mortality compared to untreated patients, suggesting limited efficacy in this context.

The study found no major differences in other serious complications between IVIG-treated and untreated patients, except for a slight advantage in the use of prone position ventilation in the IVIG group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study. Liu, J., Chen, Y., Li, R., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0889159124006482

A review of intravenous immunoglobulin in the treatment ... This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9932260/

Long-term high-dose immunoglobulin successfully treats Long ... Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05350774

Immunotherapy for Neurological Post-Acute Sequelae of ... Exploratory objective: To investigate the laboratory effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV ...

4. pharmacytimes.com pharmacytimes.com/view/ivig-demonstrates-effectiveness-in-several-neuroimmune-conditions-indicating-potential-for-long-covid-treatment

IVIG Demonstrates Effectiveness in Several Neuroimmune ... Intravenous immunoglobulin (IVIG) has proven efficacy in autoimmune neuropathies, with mixed but promising outcomes in severe COVID-19 cases.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9900022/

An updated systematic review and meta-analysis - PMC Results of this study suggest that severe hospitalized COVID-19 patients treated with high-dose IVIg would have a lower risk of death than patients with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9392972/

A potential treatment for the post-acute sequelae of SARS ... Pregnant women experiencing severe symptoms of PASC could be included in the trial, as IVIG is FDA pregnancy category C, generally considered safe in pregnancy ...