IVIG (Gamunex-C) Treatment Study for POTS Subjects

Postural Tachycardia Syndrome Clinical Trial

— iSTAND  

Official title:

IVIG (Gamunex-C) Study of Treatment for Autoimmune Neuropathic Dysautonomia/Postural Tachycardia (POTS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03919773
• Other study ID #: STU-2018-0005
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 29, 2018
• Est. completion date: December 1, 2023

Study information

• Verified date: March 2024
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 1, 2023
• Est. primary completion date: June 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Postural Orthostatic Tachycardia Syndrome
• Postural Tachycardia Syndrome
• Tachycardia

Intervention

Drug:
• 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.
• Albumin
This will be the matching placebo used in the study.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Dysautonomia International, Grifols Biologicals, LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in symptoms measured by change in COMPASS-31 score.	Primary outcome with POTS symptoms	12 weeks