Trial Report Randomized controlled trial of intravenous immunoglobulin for autoimmune postural orthostatic tachycardia syndrome (iSTAND)

Abstract
Objective: This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS).

Background: POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted.

Methods: This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion.

Results: A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups.

Conclusions: This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.

Keywords: Albumin; Clinical trial; Dysautonomia; IVIG; Postural orthostatic tachycardia syndrome (POTS).

https://pubmed.ncbi.nlm.nih.gov/38311655/

 

I think the researchers acknowledged this somewhere, but albumin has immune-modulating properties, so it’s not an ideal choice as a placebo.

 

I doubt it has very much - I was not aware of any.
Given the large amount of circulating albumin anyway I doubt the infusions produced a major percentage change.

I not quite sure what the figures mean but the change in score with IVIG actually seems to be only half that with albumin. I think it likely that the changes seen are due to non-specific factors relating to the trial context.

 

Yes strange that IVIG had the lowest decrease in mean score but the highest percentage of improvers.

The following figure is from their pre-print.

 

I can’t find it again, but I read an article in which a researcher from the early days of IVIg described how they used IV albumin as a placebo, then were surprised to discover that it wasn’t inactive in terms of immune-modulating effects when they analysed blood samples. [Link now added below]

Here’s a different article that mentions it:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692529/

Edited to add: This was brought to my attention by a researcher who is connected to the group who did the study, although she is not one of the authors.

Edited to clarify: She told me this in general correspondence, not in regards to this particular study.

Edited to add link to study that I couldn't find:
https://onlinelibrary.wiley.com/doi/10.1111/j.1423-0410.2011.01475.x
It is behind a paywall but available on Sci Hub.

Sorry for all the edits. Please forgive my 80-plus brain.

 

And there is also mention of “endothelial stabilization”, which sounds like it could be helpful in POTS.

https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1412827

(Behind paywall)