Pyridostigmine for Postural Tachycardia Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Phillip A. Low, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Mayo Clinic

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a 3-day study comparing pyridostigmine versus placebo in the treatment of postural tachycardia syndrome (POTS). The researchers expect pyridostigmine to improve tachycardia and stabilize blood pressure.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but you cannot take medications that interfere with autonomic testing or have taken pyridostigmine in the past month.

What data supports the idea that Pyridostigmine for Postural Tachycardia Syndrome is an effective drug?

The available research shows that Pyridostigmine can be an effective treatment for Postural Tachycardia Syndrome. In one study, a child with severe symptoms who did not respond to other treatments showed a positive response to Pyridostigmine, with improvements lasting for 9 months without needing additional blood pressure medication. Another case reported a 34-year-old woman who experienced significant symptom relief after four months of Pyridostigmine treatment, allowing her to work as a nurse. These examples suggest that Pyridostigmine can help reduce symptoms like dizziness and palpitations in people with this condition.

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What safety data exists for pyridostigmine in treating postural tachycardia syndrome?

Pyridostigmine has been studied for safety in treating postural tachycardia syndrome (POTS). In a study involving a child with POTS, pyridostigmine was administered without major adverse effects, showing a favorable response and persistent positive effects over 9 months. Another report from a single-center experience indicated the need for further clarity on long-term efficacy and adverse effects. Additionally, a case of pyridostigmine overdose in a myasthenia gravis patient showed that toxicity is self-limiting and manageable with prompt treatment, though caution is advised for potential cardiac effects, especially in elderly patients. Overall, pyridostigmine appears to be a safe treatment option for POTS with careful monitoring.

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Is the drug Pyridostigmine a promising treatment for Postural Tachycardia Syndrome?

Yes, Pyridostigmine is a promising treatment for Postural Tachycardia Syndrome. It has shown positive effects in patients, helping to reduce symptoms like dizziness and palpitations, and allowing them to function better in daily life. It has been effective in both children and adults, with no major side effects reported in the studies.

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Eligibility Criteria

This trial is for individuals with Postural Tachycardia Syndrome (POTS), characterized by a rapid increase in heartbeat upon standing. Participants must experience symptoms like weakness, dizziness, blurry vision, nausea, heart palpitations, and concentration issues. Pregnant or breastfeeding women, those with thyroid disorders, significant heart disease or other illnesses affecting the autonomic system are excluded.

Inclusion Criteria

You have a condition called postural tachycardia syndrome, which is diagnosed when your heart rate goes up by 30 or more beats per minute within 5 minutes of standing up.

You have been diagnosed with postural tachycardia syndrome.

Your heart rate increases by 30 or more beats per minute within 5 minutes of standing up.

Exclusion Criteria

Pregnant or lactating women

You have a thyroid condition that is not under control.

You have a serious illness or organ problems that could affect how your body functions, or you may have trouble following study instructions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive either placebo or 180 mg pyridostigmine in time release formulation for 3 days

3 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Participant Groups

The study tests pyridostigmine against a placebo over three days to see if it can reduce the fast heartbeat and stabilize blood pressure in POTS patients. The goal is to determine whether pyridostigmine is effective in treating symptoms of POTS compared to an inactive substance.

Group I: pyridostigmine Active Control 1 Intervention

Active study drug

Group II: Placebo Placebo Group 1 Intervention

Control

Pyridostigmine is already approved in United States, Canada, European Union for the following indications:

🇺🇸 Approved in United States as Mestinon for:

• Myasthenia Gravis
• Dysautonomia
• Reversal of Nondepolarizing Muscle Relaxants
• Nerve Agent Pretreatment

🇨🇦 Approved in Canada as Mestinon for:

• Myasthenia Gravis
• Dysautonomia
• Reversal of Nondepolarizing Muscle Relaxants

🇪🇺 Approved in European Union as Mestinon for:

• Myasthenia Gravis
• Dysautonomia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic Rochester, MN

Who Is Running the Clinical Trial?

Mayo Clinic Lead Sponsor

National Institute of Neurological Disorders and Stroke (NINDS) Collaborator

National Institutes of Health (NIH) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of pyridostigmine in a child with postural tachycardia syndrome. [2013] Pyridostigmine has been proposed for the treatment of postural orthostatic tachycardia syndrome in adults at a dose of 60 mg twice daily, but no dosing recommendation exists for children. With the approval of our local ethics board, we tested the pharmacokinetics of pyridostigmine in 6 children with myasthenia and a pediatric index patient with severe postural orthostatic tachycardia syndrome whose condition failed all conventional therapy and who had developed significant postural hypertension. Pyridostigmine was quantified by using a validated, semiautomated, and specific high-performance liquid chromatography/tandem mass spectrometry assay in combination with online column-switching extraction and turbo electrospray ionization. The patient with postural orthostatic tachycardia syndrome showed a dose-dependent favorable response to oral pyridostigmine. Pharmacokinetic evaluation revealed a short half-life of 2.29 hours, similar to the 2.0 +/- 0.63 hours in the patients with myasthenia. The patient with postural orthostatic tachycardia syndrome has subsequently been treated at a dose of 45 mg in the morning, 30 mg at lunchtime, and 15 mg at bedtime; after 9 months, there has been persistent positive effect and without additional blood pressure medication. No major adverse effects occurred. Pyridostigmine has been a safe and effective treatment modality for this child with postural orthostatic tachycardia syndrome. The short half-life suggests that dosing 3 times per day is preferable.

2. United States pubmed.ncbi.nlm.nih.gov

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. [2013] The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients.

3. Turkey pubmed.ncbi.nlm.nih.gov

[Pyridostigmine in the treatment of postural orthostatic tachycardia syndrome]. [2018] A 34-year-old female patient was admitted with the complaints of inability to stand upright, palpitations, dizziness, and fatigue in the upright posture for the last one year. She was found to stand upright for less than one minute without symptoms. Tilt table testing showed that, compared to baseline her heart rate increased 55 beats/min in the fifth minute of the test with the symptoms of palpitations, fatigue and sweating without any significant change in her blood pressure. Postural orthostatic tachycardia syndrome was diagnosed, and pyridostigmine treatment was started. Four months after treatment her symptoms were relieved so that she was able to function as a nurse.

4. United States pubmed.ncbi.nlm.nih.gov

Pyridostigmine in the treatment of orthostatic intolerance. [2013] To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance.

5. England pubmed.ncbi.nlm.nih.gov

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association. [2022] Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with

6. United States pubmed.ncbi.nlm.nih.gov

Pyridostigmine Suicidal Attempt in a Myasthenia Gravis Patient. [2020] BACKGROUND Pyridostigmine is a quaternary amine parasympathomymetic which inhibits acetylcholinesterase for the treatment of various conditions such as myasthenia gravis. Previously, no cases of pyridostigmine toxicity in human beings have been reported except the cases reported among the troops of Persian Gulf War. CASE REPORT A 47-year-old female intentionally ingested a high dose of pyridostigmine (Mestinon) and developed its toxic symptoms within 1 hour of ingestion. She was treated with injections of atropine and pralidoxime. The patient made an excellent recovery and responded to the classical treatment using atropine and pralidoxime. She was discharged on the second day of admission. CONCLUSIONS The authors demonstrated that pyridostigmine poisoning is self-limiting and well tolerated by young adults; however, unwanted effects of pyridostigmine on the heart has still to be considered which may become profound to the point of generating heart failure, syncope, or stress particularly in elderly patients. As the literature on human toxicity with pyridostigmine is scarce, not much data is available on its toxicity. However, prompt and specific management of pyridostigmine toxicity promises safety.