Postural Tachycardia SyndromePhase 1/2iSTANDNCT03919773
IVIG (Gamunex-C) Treatment Study for POTS Subjects
A Phase 1/2 study testing IVIG and Albumin in people with Postural Tachycardia Syndrome, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postural Tachycardia Syndrome
- What is being tested?
- IVIG and Albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2018to 1 Dec 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: IVIG (Gamunex-C) Study of Treatment for Autoimmune Neuropathic Dysautonomia/Postural Tachycardia (POTS)
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.
Read the 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.
- Conditions
- Postural Tachycardia Syndrome
- Being tested
- IVIG, Albumin
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVIGDrug
Also called intravenous immunoglobulin
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.
AlbuminDrug
This will be the matching placebo used in the study.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 Receives: Drug: Albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline,13 weeks
Secondary outcomes (1)
Number of Participants With Clinical Improvement
The count of participants with clinical improvement at 13 weeks is being reported here. Clinical improvement was defined as a reduction of the COMPASS-31 total score by 20% or more. Lower scores are associated with improvement and a 20% reduction was used as a meaningful change in previous studies of POTS
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2019
- Study start29 Oct 2018
- Primary completion26 Jun 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postural Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- double-blind randomized controlled crossover pilot study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Grifols Biologicals, LLC, Dysautonomia International
- Responsible party
- Principal investigator, Steven Vernino MD PhD, University of Texas Southwestern Medical Center
- Investigators
- Steven Vernino, MD, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03919773
- Sponsor's protocol ID
- STU-2018-0005
- Acronym
- iSTAND
- Status last verified
- Sep 2024
- First submitted
- 5 Feb 2019
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: All patient information will be de-identified if sent out. Any AE and/or SAE will be sent out for review.
Publications
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.
PubMed 28644253
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IVIG (Gamunex-C) Study of Treatment for Autoimmune Neuropathic Dysautonomia/Postural Tachycardia (POTS)
- ClinicalTrials.gov ID
- NCT03919773
- Acronym / sponsor ID
- iSTAND / STU-2018-0005
- Conditions
- Postural Tachycardia Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Grifols Biologicals, LLC, Dysautonomia International
- Study start
- 29 Oct 2018 (actual)
- Primary completion
- 26 Jun 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 18 Apr 2019 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind randomized controlled crossover pilot study
| Arm | Type | Receives |
|---|---|---|
| Treatment IVIG Arm | Active comparator | Drug: IVIGIVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total). |
| Treatment Albumin Arm | Placebo comparator | Drug: Albuminalbumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- Stable oral medical therapy for past 3 months
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVIGAlso: intravenous immunoglobulinIf 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. | Drug | Treatment IVIG Arm |
| AlbuminThis will be the matching placebo used in the study. | Drug | Treatment Albumin Arm |
Primary outcome
Change in Symptoms Measured by Change in COMPASS-31 Score (After Initial Treatment Phase)
Time frame: Baseline,13 weeks
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.
1 secondary outcome
Number of Participants With Clinical Improvement
Time frame: 13 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28644253Goodman 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.
- Individual participant dataSharing planned: No. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Vernino, MD, PhD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IVIG and Albumin in people with Postural Tachycardia Syndrome, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Symptoms Measured by Change in COMPASS-31 Score (After Initial Treatment Phase) (time frame: Baseline,13 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03919773, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.