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History of Changes for Study: NCT03919773
IVIG (Gamunex-C) Treatment Study for POTS Subjects (iSTAND)
Latest version (submitted January 21, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 14, 2019 None (earliest Version on record)
2 May 9, 2019 Study Status, Outcome Measures, Arms and Interventions and Study Description
3 May 18, 2020 Sponsor/Collaborators and Study Status
4 May 14, 2021 Study Design, Sponsor/Collaborators, Study Status, Arms and Interventions and Eligibility
5 January 21, 2022 Study Status
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Study NCT03919773
Submitted Date:  April 14, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: STU-2018-0005
Brief Title: IVIG (Gamunex-C) Treatment Study for POTS Subjects (iSTAND)
Official Title: IVIG (Gamunex-C) Study of Treatment for Autoimmune Neuropathic Dysautonomia/Postural Tachycardia (POTS)
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2019
Overall Status: Enrolling by invitation
Study Start: October 29, 2018
Primary Completion: July 2019 [Anticipated]
Study Completion: July 2019 [Anticipated]
First Submitted: February 5, 2019
First Submitted that
Met QC Criteria:
April 14, 2019
First Posted: April 18, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
April 14, 2019
Last Update Posted: April 18, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of Texas Southwestern Medical Center
Responsible Party: Principal Investigator
Investigator: Steven Vernino
Official Title: PROFESSOR
Affiliation: University of Texas Southwestern Medical Center
Collaborators: Grifols Biologicals, LLC
Dysautonomia International
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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) (see attached package insert). 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. (See Goodman, B. P. (2017). "Immunoresponsive Autonomic Neuropathy in Sjogren Syndrome-Case Series and Literature Review." Am J Ther doi: 10.1097/MJT.0000000000000583. and Oaklander, A. L. (2016). "Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies." Neurotherapeutics 13(1): 108-117).

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.

Open or close this module Conditions
Conditions: Postural Tachycardia Syndrome
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Crossover Assignment
double-blind placebo controlled crossover pilot study
Number of Arms: 2
Masking: Triple (Participant, Care Provider, Investigator)
Allocation: Randomized
Enrollment: 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Treatment Arm
IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total).
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.

Other Names:
  • albumin
Placebo Comparator: Treatment Placebo Arm
albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during
Drug: Albumin
This will be the matching placebo used in the study.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Our primary aim is to evaluate the number of research participants that are treated with IVIG (Gammunex-C) versus active placebo (intravenous albumin) with improving the symptoms of POTS using the COMPASS-31 score.
[ Time Frame: 12 weeks ]

Primary outcome with POTS symptoms
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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 of autoimmune disease including Hashimoto's thyroiditis, celiac disease, antiphospholipid syndrome, rheumatoid arthritis, SLE, CVID or Sjogren's syndrome
    • Confirmed family history of a defined autoimmune disorder
    • 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.
  • History of IgA deficiency or evidence of IgA deficiency at screening
  • 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.
Open or close this module Contacts/Locations
Study Officials: Steven Vernino, MD, PhD
Principal Investigator
UT Southwestern Medical Center
Locations: United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75208
Open or close this module IPDSharing
Plan to Share IPD: No
All patient information will be de-identified if sent out. Any AE and/or SAE will be sent out for review.
Open or close this module References
Citations: Goodman BP, Crepeau A, Dhawan PS, Khoury JA, Harris LA. Spectrum of Autonomic Nervous System Impairment in Sjögren Syndrome. Neurologist. 2017 Jul;22(4):127-130. doi: 10.1097/NRL.0000000000000134. PubMed 28644253
Links:
Available IPD/Information:

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