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Mestinon Clinical Trial

The purpose of this clinical trial is to test the exercise response to Mestinon in people with ME/CFS.

  • David Systrom, MD

  • Clinical trial approved (Clinical Trials Number NCT03674541). 
  • Computational analysis has been completed.
  • The results have confirmed the hypothesis of how Mestinon works in ME/CFS patients on one of the pathophysiology of some ME/CFS patients.
  • The manuscript has been published on CHEST.
  • A follow-up analysis of the long-term effect of Mestinon is ongoing, and the study is expected to be completed this year.


Dr. Systrom has consistently found that some people with ME/CFS suffering from fatigue have Preload Failure (PLF). In this instance, PLF is thought to come from an imbalance in the autonomic nervous system and results in reduced filling of the heart during exertion.

Prior studies have shown that treatment with Mestinon results in symptomatic improvement in patients with PLF. Dr. Systrom intends to evaluate the short-term effects of Mestinon on the autonomic nervous system and neurovascular control in people with ME/CFS with PLF. Studying these features will improve our understanding of ME/CFS and this trial may lead to new therapeutic options for some people with ME/CFS.

More details of this trial can be found here.


Advancements in ME / CFS Research, David M. Systrom, MD

  1. Select potential candidates for the study.
  2. Enroll subjects and conduct evaluation at Brigham and Women’s Hospital.
  3. Assign subjects in a 1:1 ratio to receive a 60 mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). Perform a second iCPET was 50 minutes later.
  4. Conduct biostatistical analysis to assess:
    • the difference in peak exercise oxygen uptake (VO2)
    • exercise pulmonary and systemic hemodynamics and gas exchange.
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation®

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