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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug IVIG for treating POTS?

IVIG has been shown to be effective in treating various autoimmune and inflammatory conditions, such as Kawasaki disease, Guillain-Barré syndrome, and multiple sclerosis, by modulating the immune system. This suggests it might help with POTS, which is thought to have an immune-related component. ^{1 2 3 4 5}

Is IVIG generally safe for humans?

IVIG (Intravenous Immunoglobulin) is generally considered safe, but it can cause serious side effects affecting the kidneys, heart, skin, and blood. The risk of these side effects can depend on factors like age, health conditions, and the specific IVIG product used. It's important for doctors to carefully consider these risks before prescribing IVIG. ^{6 7 8 9 10}

How is the drug IVIG different from other treatments for POTS?

IVIG (Intravenous Immunoglobulin) is unique because it is derived from pooled human plasma and primarily consists of immunoglobulin G (IgG), which helps modulate the immune system. Unlike other treatments for POTS, which may focus on managing symptoms like heart rate and blood pressure, IVIG is used to address underlying immune dysfunction, although its use in POTS is still being studied. ^{1 11 12 13 14}

What is the purpose of this trial?

This trial aims to see if IVIG can help people with POTS who have autoimmune issues. IVIG is a treatment made from donated blood that gives extra antibodies to help control the immune system. The study will test if this treatment can improve symptoms in these patients. IVIG has been used for over two decades to treat various autoimmune and systemic inflammatory diseases.

Research Team

Steven Vernino, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin: new clinical applications. [2007]

2. England pubmed.ncbi.nlm.nih.gov

Using immunoglobulins in muscular disease treatment. [2019]

3. France pubmed.ncbi.nlm.nih.gov

[Immunomodulatory effects of intravenous immunoglobulins]. [2006]

4. United States pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin: implications for use in the neurological patient. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

[Intravenous immunoglobulin in multiple sclerosis]. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Risks associated with the use of intravenous immunoglobulin. [2022]

7. United States 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. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Octagam® for chronic inflammatory demyelinating polyneuropathy: results from three observational studies. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

Frequently asked questions on seven rare adverse events following immunization. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance study to assess the safety and tolerability of an Inactivated Poliomyelitis Vaccine in Indian children. [2018]

11. Mexico pubmed.ncbi.nlm.nih.gov

[Chronic kidney disease in adults with primary immunodeficiency diseases in treatment with intravenous immunoglobulin]. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Clinical uses of intravenous immune globulin. [2019]

13. Spain pubmed.ncbi.nlm.nih.gov

Immunomodulation of various autoimmune diseases by intravenous immunoglobulin. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Safety of intravenous immunoglobulin treatment. [2010]