IVIG (Gamunex-C) Treatment Study for POTS Subjects

NCT ID: NCT03919773

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-29
• Study Completion Date: 2023-12-01

Brief Summary

The purpose of this trial is to evaluate the symptomatic benefits of immunomodulatory treatment with IVIG for POTS (postural tachycardia syndrome) patients with evidence of autoimmunity.

Detailed Description

Gammunex-C, a form of intravenous immunoglobulin (IVIG), is approved for the treatment of chronic inflammatory demyelinating neuropathy (CIDP) or idiopathic thrombocytopenic purpura (ITP). IVIG has been in use for many decades in the treatment of these disorders and many other inflammatory/autoimmune diseases. It is generally very safe and well tolerated. More recently, IVIG has been proposed as an effective treatment for presumed inflammatory neurological disorders which do not meet the criteria for CIDP. Specifically, case reports and cases series have indicated therapeutic responses to IVIG in autonomic neuropathies.

Intravenous Albumin is approved for the treatment of hypovolemia (see attached package insert). The use of albumin to increase plasma volume in patients with POTS has been suggested. In this study, albumin will be used as an active control treatment to provide the same volume and protein load as IVIG but without the immunomodulatory effects.

There have been few well designed clinical therapy trials aimed at POTS patients and even fewer that are aimed at a particular pathophysiological subtype of POTS. Evidence suggests that POTS is a heterogeneous disorder with differing underlying mechanisms. Several uncontrolled case series have suggested a benefit of IVIG for POTS, but the volume expansion associated with infusion of IVIG make it difficult to assess the immunomodulatory effects of this treatment. We propose to evaluate the efficacy of IVIG using a double-blind randomized cross over design that will determine efficacy while reducing effects of inter-subject variability and placebo effect which are common problems in POTS therapy research. Even with the statistical advantages of a crossover design, the treatment cohort will be small, and this study is designed to be a pilot (phase II) study to evaluate the feasibility, tolerability and potential benefits of treatment. The results of this pilot study will provide the impetus and rationale for a larger multicenter clinical trial to definitively evaluate immunomodulatory treatment in POTS.

Conditions

Postural Tachycardia Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment IVIG Arm

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

Group Type: ACTIVE_COMPARATOR

IVIG

Intervention Type: DRUG

If you participate in this study there will be 18 scheduled treatment infusions during the 30 week study period. All the study visits and treatment visits will be outpatient visits.

Once you qualify to participate in the study and begin treatment, there will be two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each.

Treatment Albumin Arm

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

Group Type: PLACEBO_COMPARATOR

Albumin

Intervention Type: DRUG

This will be the matching placebo used in the study.

Interventions

IVIG

If you participate in this study there will be 18 scheduled treatment infusions during the 30 week study period. All the study visits and treatment visits will be outpatient visits.

Once you qualify to participate in the study and begin treatment, there will be two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each.

Intervention Type: DRUG

Albumin

This will be the matching placebo used in the study.

Intervention Type: DRUG

Other Intervention Names

intravenous immunoglobulin

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older, and able to provide informed consent
• Diagnosis of POTS (see Table 1)
• COMPASS-31 symptom score showing moderate to severe autonomic symptoms
• At least 3 of the following clinical or laboratory features of autoimmunity

• One or more serum autoantibodies (ANA ≥ 1:160, gAChR antibody > 0.2 nmol/L, positive ENA, aPL, TTG, gliadin) or inflammatory markers (ESR > 30, CRP > 2, low C3 complement or low immunoglobulin IgG level)
• Confirmed personal history or family history of defined autoimmune disease including Hashimoto's thyroiditis, celiac disease, antiphospholipid syndrome, rheumatoid arthritis, SLE, or Sjogren's syndrome
• Clear history of acute or subacute onset following infection, immunization, injury/concussion, surgery or pregnancy.
• Evidence of esophageal, gastric or intestinal dysmotility (with weight loss)
• Evidence of small fiber neuropathy (abnormal QSART or IENFD)
• Stable oral medical therapy for past 3 months
• Ambulatory at time of screening

Exclusion Criteria

• Current or previous immunosuppression therapy or IVIG treatment
• Contraindication to intravenous immunoglobulin or intravenous albumin
• Known allergic reactions to blood products including intravenous immunoglobulin (IVIG) and/or subcutaneous immunoglobulin (SCIG), such as history of clinically relevant hemolysis after IVIG infusion, aseptic meningitis, recurrent severe headache, hypersensitivity, severe generalized or severe local skin reaction.
• Inadequate peripheral venous access
• Evidence of renal insufficiency (Cr > 1.5 x elevated) or liver disease (transaminases > 2.5x upper limit) at screening
• History of thrombotic episode within 3 years of enrollment
• Other major medical issue which, in investigators opinion, increases risk for adverse event over the next 12 months or may require separate management.
• Female patients who are premenopausal and are (a) pregnant based on serum pregnancy test, or (b) breast-feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Biologicals, LLC

INDUSTRY

Sponsor Role: collaborator

Dysautonomia International

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Steven Vernino MD PhD

PROFESSOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Vernino, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

Goodman BP, Crepeau A, Dhawan PS, Khoury JA, Harris LA. Spectrum of Autonomic Nervous System Impairment in Sjogren Syndrome. Neurologist. 2017 Jul;22(4):127-130. doi: 10.1097/NRL.0000000000000134.

Reference Type: BACKGROUND

PMID: 28644253 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

STU-2018-0005

Identifier Type: -

Identifier Source: org_study_id