IVIG for POTS

(iSTAND Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Immunosuppressants, IVIG

Disqualifiers: Renal insufficiency, Liver disease, Thrombotic episode, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called IVIG (Intravenous Immunoglobulin) to determine its effectiveness for people with POTS, a condition causing rapid heartbeat upon standing, particularly in those with signs of autoimmunity. IVIG is administered through infusions and is compared to a placebo using albumin. The trial seeks participants diagnosed with POTS who experience moderate to severe symptoms and show signs of autoimmunity, such as specific antibodies or a family history of autoimmune diseases. Participants should maintain stable treatment routines and be able to walk unaided. As a Phase 1, Phase 2 trial, it aims to understand how IVIG works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial requires that you have been on stable oral medical therapy for the past 3 months, so you should not stop taking your current medications if they have been stable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IVIG (intravenous immunoglobulin) has been safely used for many years to treat various inflammatory and autoimmune diseases. In a small study on postural tachycardia syndrome (POTS), researchers compared IVIG to albumin infusions and found no major safety differences. Other studies suggest that patients generally tolerate IVIG well. Some might experience mild side effects, such as headaches or low-grade fevers, but serious side effects are rare. Overall, IVIG has a strong safety record, making it a promising option for conditions like POTS. ^{1 2 3 4 5}

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

Unlike the standard treatments for Postural Orthostatic Tachycardia Syndrome (POTS), which often include medications like beta-blockers and lifestyle changes, IVIG (intravenous immunoglobulin) offers a unique approach by targeting the immune system. Researchers are excited about IVIG because it uses antibodies derived from healthy donors to potentially modulate immune responses and reduce inflammation, which may be underlying factors in POTS. This treatment could provide relief for patients who do not respond to current medications, offering a new avenue for managing symptoms more effectively.

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

Research suggests that IVIG (intravenous immunoglobulin), which participants in this trial may receive, might help some patients with severe, hard-to-treat POTS (postural orthostatic tachycardia syndrome) by reducing symptoms and improving daily function. One study showed that patients receiving treatments like IVIG experienced noticeable improvements in their POTS symptoms. However, another small study found no significant difference when comparing IVIG to a placebo using albumin, the comparator in this trial. This indicates that the effectiveness of IVIG for POTS remains uncertain, though hopeful signs exist for some patients. More research is needed to confirm its benefits specifically for POTS. ^{1 2 3 6 7}

Who Is on the Research Team?

Steven Vernino, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with POTS who have moderate to severe autonomic symptoms and signs of autoimmunity, such as certain autoantibodies or a personal/family history of autoimmune diseases. Participants must be stable on current medications and able to walk. Pregnant or breastfeeding women, those with poor vein access, previous immunosuppression therapy or IVIG treatment, allergies to blood products, kidney/liver disease, recent thrombosis, or other major medical issues are excluded.

Inclusion Criteria

I or someone in my family has an autoimmune disease like Hashimoto's, celiac, or rheumatoid arthritis.

I have high levels of certain antibodies or markers indicating inflammation.

I can walk by myself at the time of screening.

Exclusion Criteria

I have poor vein access for IVs.

I am currently on or have had immunosuppression therapy or IVIG treatment.

I am a premenopausal woman who is either pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IVIG (Gamunex-C) or albumin infusions every week for 4 weeks, then every 2 weeks for 8 weeks

12 weeks

Weekly visits for 4 weeks, then bi-weekly visits for 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• IVIG

Trial Overview The study tests if IVIG (Gamunex-C), an immune-modulating treatment, can relieve symptoms in POTS patients showing signs of autoimmunity. It compares the effects of IVIG against Albumin (a plasma protein solution) in improving patient conditions.

How Is the Trial Designed?

Group I: Treatment IVIG Arm Active Control 1 Intervention

IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total).

Group II: Treatment Albumin Arm Placebo Group 1 Intervention

albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during

IVIG is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Intravenous Immunoglobulin for:

• Primary immunodeficiency diseases
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Multifocal motor neuropathy
• Kawasaki disease
• Immune thrombocytopenic purpura (ITP)

Approved in European Union as Intravenous Immunoglobulin for:

• Primary immunodeficiency syndromes
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Multifocal motor neuropathy
• Kawasaki disease
• Immune thrombocytopenic purpura (ITP)

Approved in Canada as Intravenous Immunoglobulin for:

• Primary immunodeficiency diseases
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Multifocal motor neuropathy
• Kawasaki disease
• Immune thrombocytopenic purpura (ITP)

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Grifols Biologicals, LLC

Industry Sponsor

Trials

33

Recruited

9,500+

Dysautonomia International

Collaborator

Trials

6

Recruited

420+

Published Research Related to This Trial

Intravenous immune globulin (IVIG) is primarily composed of immunoglobulin G (IgG) and is effective in treating conditions like idiopathic thrombocytopenic purpura (ITP) and primary humoral immunodeficiencies (PHI), with specific dosages recommended for each condition.

While IVIG is a valuable treatment option for various immunodeficiencies and autoimmune disorders, its high cost and the need for more conclusive efficacy data in some conditions are important considerations for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical uses of intravenous immune globulin. Knapp, MJ., Colburn, PA.[2019]

In a study of 35 adults with humoral primary immunodeficiency diseases receiving intravenous immunoglobulin (IVIG), 51.4% showed signs of kidney damage, highlighting a significant risk associated with long-term IVIG treatment.

Patients treated with IVIG for more than 5 years had a higher incidence of chronic kidney disease (55.6%), indicating the need for regular kidney function monitoring and consideration of using sugar-free immunoglobulin to mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic kidney disease in adults with primary immunodeficiency diseases in treatment with intravenous immunoglobulin]. O'Farrill-Romanillos, PM., Luna-Mújica, RF., Contreras-García, CE., et al.[2021]

While IGIV products are generally considered safe, many clinical studies have been small and may not fully capture the incidence of adverse events, which can include serious complications affecting various organ systems.

Clinicians should carefully evaluate the risks and benefits of IGIV therapy, considering factors like patient age and underlying health conditions, and should only prescribe these products for conditions with strong evidence of efficacy from well-controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks associated with the use of intravenous immunoglobulin. Pierce, LR., Jain, N.[2022]

A review of 41,792 adverse event reports related to inactivated poliovirus vaccine (IPV) from 2000 to 2012 found that 95% of reports were for children under 7 years, with the majority being non-serious events, indicating a favorable safety profile for IPV.

The analysis showed no new or unexpected safety issues associated with IPV, and reports of sudden infant death syndrome were consistent with patterns seen in other vaccines, suggesting that IPV does not pose additional risks compared to other immunizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000-12. Iqbal, S., Shi, J., Seib, K., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03919773

IVIG (Gamunex-C) Treatment Study for POTS Subjects The purpose of this trial is to evaluate the symptomatic benefits of immunomodulatory treatment with IVIG for POTS (postural tachycardia syndrome) patients with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38311655/

Randomized controlled trial of intravenous immunoglobulin ... This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion.

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03919773?type=Intr&cond=Postural+Orthostatic+Tachycardia+Syndrome&lupd_s=04%2F04%2F2019&lupd_d=14

IVIG (Gamunex-C) Treatment Study for POTS Subjects The purpose of this trial is to evaluate the symptomatic benefits of immunomodulatory treatment with IVIG for POTS (postural tachycardia syndrome) patients with ...

4. frontiersin.org frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1647203/full

Immunotherapies for postural orthostatic tachycardia ... A placebo-controlled clinical trial was conducted for efgartigimod in 53 patients with post-COVID POTS, but preliminary outcomes showed no benefit of ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36008726/

Immunotherapy with subcutaneous immunoglobulin or ... Patients with severe, treatment-refractory POTS experienced significant functional improvement with reduction in the autonomic symptoms following immunotherapy ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2589909021000320

Maintenance therapy with subcutaneous immunoglobulin ... These findings suggest that autoimmune-mediated neuropathic PoTS can be treated sufficiently with IVIg whereas SCIg minimizes side-effects.

7. neurology.org neurology.org/doi/10.1212/01.wnl.0000903548.26150.37

Immunotherapy With Subcutaneous Immunoglobulin or ... This case series suggests that SCIG and PLEX may be safe and effective treatments for patients with severe POTS refractory to standard therapies.