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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03919773
Recruitment Status : Enrolling by invitation
First Posted : April 18, 2019
Last Update Posted : January 24, 2022
Sponsor:
Collaborators:
Grifols Biologicals, LLC
Dysautonomia International
Information provided by (Responsible Party):
Steven Vernino, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE February 5, 2019
First Posted Date  ICMJE April 18, 2019
Last Update Posted Date January 24, 2022
Actual Study Start Date  ICMJE October 29, 2018
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
Improvement in symptoms measured by change in COMPASS-31 score. [ Time Frame: 12 weeks ]
Primary outcome with POTS symptoms
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2019)
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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IVIG (Gamunex-C) Treatment Study for POTS Subjects
Official Title  ICMJE IVIG (Gamunex-C) Study of Treatment for Autoimmune Neuropathic Dysautonomia/Postural Tachycardia (POTS)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
double-blind randomized controlled crossover pilot study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
double-blind
Primary Purpose: Treatment
Condition  ICMJE Postural Tachycardia Syndrome
Intervention  ICMJE
  • 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
  • Drug: Albumin
    This will be the matching placebo used in the study.
Study Arms  ICMJE
  • Active Comparator: 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).
    Intervention: Drug: IVIG
  • Placebo Comparator: 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
    Intervention: Drug: Albumin
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: May 14, 2021)
32
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2019)
20
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03919773
Other Study ID Numbers  ICMJE STU-2018-0005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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.
Current Responsible Party Steven Vernino, University of Texas Southwestern Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Grifols Biologicals, LLC
  • Dysautonomia International
Investigators  ICMJE
Principal Investigator: Steven Vernino, MD, PhD UT Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP