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

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03919773

Collaborator

Grifols Biologicals, LLC (Industry), Dysautonomia International (Other)

Enrollment

Location

Arms

61.1

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

double-blind randomized controlled crossover pilot studydouble-blind randomized controlled crossover pilot study

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

double-blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 29, 2018

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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).	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: intravenous immunoglobulin
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	Drug: Albumin This will be the matching placebo used in the study.

Arm

Intervention/Treatment

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).

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:

intravenous immunoglobulin

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

Drug: Albumin

This will be the matching placebo used in the study.

Outcome Measures

Primary Outcome Measures

Improvement in symptoms measured by change in COMPASS-31 score. [12 weeks]
Primary outcome with POTS symptoms

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.