IVIG (Gamunex-C) Treatment Study for POTS Subjects

NCT03919773 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: STU-2018-0005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Postural Tachycardia Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in Symptoms Measured by Change in COMPASS-31 Score (After Initial Treatment Phase)

  Primary outcome was change in autonomic symptom burden, assessed by total COMPASS-31 (sum of scaled subscores), comparing assessment at week 13 (2 weeks after final infusion) minus the assessment at baseline. This questionnaire generates a weighted score from 0 to 100, and questions fall into one of six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor function. A COMPASS-31 (Composite Autonomic Symptom Score-31) score of ≥20 suggests moderate-to-severe autonomic dysfunction. Higher scores indicate more severe symptoms. A reduction in score (negative change over time) indicates better outcome or response to treatment.

  Baseline,13 weeks

Secondary Outcomes (1)

• Number of Participants With Clinical Improvement

  13 weeks

Study Arms (2)

Treatment IVIG Arm

ACTIVE COMPARATOR

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

Treatment Albumin Arm

PLACEBO COMPARATOR

albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during

Drug: Albumin

Interventions

IVIG DRUG

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.

Also known as: intravenous immunoglobulin

Treatment IVIG Arm

Albumin DRUG

This will be the matching placebo used in the study.

Treatment Albumin Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Grifols Biologicals, LLC: collaborator
• Dysautonomia International: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75208, United States

Location

Related 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.

  PMID: 28644253 BACKGROUND

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Interventions

Immunoglobulins, Intravenous; Albumins

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Steven Vernino
• Organization: UT Southwestern Medical Center

steven.vernino@utsouthwestern.edu

214-648-8816

Study Officials

• Steven Vernino, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Model Details: double-blind randomized controlled crossover pilot study

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: April 18, 2019
• Study Start: October 29, 2018
• Primary Completion: June 26, 2023
• Study Completion: December 1, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)