This is the PoTS instalment of this week’s clinical trial update series. Yesterday: Long COVID. Today: PoTS.
A reminder before we start of something worth holding throughout this piece. PoTS has no approved pharmacological treatment. Every drug currently prescribed for it is being used off-label, meaning it was approved for a different condition and is being repurposed based on clinical experience and relatively small studies. The trials below represent the most serious attempts yet to change that.
Treatments that have not worked as hoped
RECOVER-AUTONOMIC (Ivabradine)
This trial was one of the most anticipated in the PoTS and Long COVID autonomic dysfunction space. It tested ivabradine, a heart rate-lowering drug that works through a different mechanism to beta blockers, in Long COVID patients with PoTS. Results were presented at the American College of Cardiology Annual Conference in March 2026, with the full paper still pending publication.
What has been shared publicly is that ivabradine reduced standing heart rate in Long COVID PoTS patients, which is consistent with its known mechanism. Whether it improved symptoms meaningfully is the detail that will become clearer when the full paper publishes. Early signals suggest the heart rate reduction did not translate straightforwardly into symptom improvement, which is consistent with what we know about PoTS: heart rate is not the only thing that matters, and reducing it does not necessarily address the underlying autonomic dysfunction driving the full symptom picture.
A separate 2026 crossover trial comparing propranolol, ivabradine, and placebo in PoTS patients found that both drugs reduced standing heart rate to a similar degree, but neither clearly outperformed the other on symptom measures. Ivabradine showed some advantages in quality of life scores. The question of which drug to reach for first in PoTS remains genuinely open.
Trials with promising or emerging evidence
REGN7544 (Regeneron) — Phase 2
This is the first clinical trial funded by a pharmaceutical company and designed specifically for PoTS rather than repurposing an existing drug. REGN7544 is a monoclonal antibody that targets NPR1, a receptor involved in regulating blood volume and vascular tone. When NPR1 is blocked, the body retains more fluid, which directly addresses the hypovolemic component of PoTS.
Phase 1 results showed REGN7544 durably increased blood pressure by 5 to 10mmHg and produced biomarker changes consistent with increased plasma volume, with no major safety signals. The Phase 2 trial (NCT06593600) is running across US and Canadian sites. Results are not expected until at least 2027. The trial requires participants to stop most existing PoTS medications during the study period, which is a significant barrier for those who are currently managing on medication. But the fact that a major pharmaceutical company has designed a trial specifically around PoTS biology is a landmark in itself.
IVIG and immunotherapy — the iSTAND trial
The iSTAND trial at UT Southwestern was the first double-blind randomised controlled trial of intravenous immunoglobulin in PoTS patients with autoimmune features. It completed in 2023 and results are anticipated to be published imminently. Given what we know about the autoimmune hypothesis in PoTS, the IVIG findings could be transformative for a subset of patients.
Ahead of those results, the case series evidence for immunotherapy in PoTS is striking. A study published in Neurology found that in seven patients with severe, refractory PoTS treated with either subcutaneous immunoglobulin (SCIG) or therapeutic plasma exchange, all seven improved. The average reduction in autonomic symptom burden was 50%, functional ability scores improved by 217%, and five of the seven returned to work or school. These are very small numbers and not from a controlled trial, but the effect sizes are large enough to take seriously while we wait for iSTAND results.
Low dose naltrexone — Calgary pilot RCT
A pilot randomised controlled trial of LDN specifically in PoTS patients is underway at the University of Calgary. This is the first properly controlled trial of a drug that many PoTS patients are already using off-label. The anti-inflammatory mechanism is coherent with what we know about immune dysregulation in PoTS, the case series evidence is encouraging, and the results, expected in 2030, will provide the first properly controlled evidence for or against its use.
Time-restricted eating — a dietary trial worth watching
A 2025 pilot study in Scientific Reports of 20 PoTS patients found that limiting food intake to an 8 to 10 hour window daily produced an average 11 bpm reduction in standing heart rate, significant improvements in fatigue, gastrointestinal symptoms and insomnia, and measurable increases in mitochondrial ATP production. The study was small and uncontrolled, but the mechanism is biologically plausible and the effect size on heart rate was comparable in magnitude to some pharmacological interventions. A larger, properly controlled dietary trial in PoTS would be a logical next step and does not yet exist.
Vagus nerve stimulation — transcutaneous auricular
A 2024 randomised controlled trial of 57 post-COVID PoTS patients found significant reductions in postural tachycardia at one month, maintained at one year follow-up, using a transcutaneous auricular vagus nerve stimulation device worn for one hour daily. This is non-invasive, drug-free, home-administered, and the one-year durability finding is encouraging. A larger trial combining vagus nerve stimulation with slow-paced breathing is now underway. The device used (Parasym) is commercially available but expensive and not NHS-funded for PoTS.
The honest summary
The PoTS trial landscape in 2026 is more active than at any previous point in the condition’s history, driven largely by the surge in post-COVID cases. But the evidence base remains limited. The strongest candidates for changing clinical practice are REGN7544 if Phase 2 confirms the Phase 1 signal, iSTAND if the results support immunotherapy in the autoimmune subgroup, and the SCIG case series if replicated in a controlled trial. LDN, vagus nerve stimulation, and time-restricted eating all have mechanistically coherent evidence at the case series or small trial level. None has yet crossed the threshold of large, properly powered, replicated evidence.
The distance between where the research is and where clinical practice is has never been wider. Patients are managing with off-label drugs, dietary modifications, and compression garments while waiting for the science to produce something better. The trials above are that something better, in progress.
The views and opinions expressed in Dysautonomia Decoded are my own and do not represent those of my employer or any affiliated organisation.
References
REGN7544 Phase 2 trial for POTS. NCT06593600. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT06593600
iSTAND Trial. IVIG treatment study for POTS subjects. NCT03919773. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03919773
Nelson C, Kesterson S, Schofield J, Blitshteyn S. Immunotherapy with subcutaneous immunoglobulin or plasmapheresis in patients with postural orthostatic tachycardia syndrome. Neurology. 2022.
Stavrakis S, et al. Noninvasive vagus nerve stimulation in postural tachycardia syndrome. JACC: Clinical Electrophysiology. 2024;10(2):346–355. https://doi.org/10.1016/j.jacep.2023.09.015
Dzotsi M, et al. Time-restricted eating improves quality of life, heart rate, and mitochondrial function in POTS. Scientific Reports. 2025;15:34345. https://doi.org/10.1038/s41598-025-19157-4
JACC: Advances. A randomized crossover trial of ivabradine, propranolol, and placebo in postural orthostatic tachycardia syndrome. 2026. https://doi.org/10.1016/j.jacadv.2026.102795
Pierson BC, et al. Oral medications for the treatment of postural orthostatic tachycardia syndrome: a systematic review. Frontiers in Neurology. 2025;15:1515486. https://doi.org/10.3389/fneur.2024.1515486