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IVIG (Gamunex-C) Treatment Study for POTS Subjects (iSTAND)

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ClinicalTrials.gov Identifier: NCT03919773
Recruitment Status : Enrolling by invitation
First Posted : April 18, 2019
Last Update Posted : May 13, 2019
Sponsor:
Collaborators:
Grifols Biologicals, LLC
Dysautonomia International
Information provided by (Responsible Party):
Steven Vernino, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Postural Tachycardia Syndrome Drug: IVIG Drug: Albumin Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: double-blind placebo controlled crossover pilot study
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: double-blind placebo controlled
Primary Purpose: Treatment
Official Title: IVIG (Gamunex-C) Study of Treatment for Autoimmune Neuropathic Dysautonomia/Postural Tachycardia (POTS)
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rhophylac

Arm Intervention/treatment
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 Name: intravenous immunoglobulin

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.




Primary Outcome Measures :
  1. Improvement in symptoms measured by change in COMPASS-31 score. [ Time Frame: 12 weeks ]
    Primary outcome with POTS symptoms



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03919773


Locations
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United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75208
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Grifols Biologicals, LLC
Dysautonomia International
Investigators
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Principal Investigator: Steven Vernino, MD, PhD UT Southwestern Medical Center

Publications:
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Responsible Party: Steven Vernino, PROFESSOR, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03919773     History of Changes
Other Study ID Numbers: STU-2018-0005
First Posted: April 18, 2019    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All patient information will be de-identified if sent out. Any AE and/or SAE will be sent out for review.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Tachycardia
Postural Orthostatic Tachycardia Syndrome
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Pathologic Processes
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Immunoglobulins
Immunoglobulins, Intravenous
gamma-Globulins
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs