Pyridostigmine for Postural Tachycardia Syndrome

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Pyridostigmine, Autonomic drugs

Disqualifiers: Pregnancy, Organ failure, Thyroid disorders, Coronary disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 3 days

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called pyridostigmine to determine its effectiveness for people with postural tachycardia syndrome (POTS). POTS can cause symptoms such as feeling faint, experiencing a fast heartbeat, or feeling lightheaded when standing. The trial compares pyridostigmine to a placebo (a sugar pill with no active medicine) to assess its effectiveness in managing these symptoms. Individuals who often feel dizzy or have a fast heartbeat upon standing might be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pyridostigmine treats postural tachycardia syndrome (POTS). Although the FDA hasn't approved it specifically for POTS, studies suggest it might alleviate symptoms like a fast heart rate. Pyridostigmine is usually well-tolerated and is already approved for other conditions, such as myasthenia gravis, so its safety has been well-studied for those uses. Some people with POTS have experienced improvements with pyridostigmine. However, not everyone tolerates it well, so discussing possible side effects with a doctor is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for POTS?

Pyridostigmine is unique for Postural Tachycardia Syndrome (POTS) because it enhances communication between nerves and muscles by inhibiting the breakdown of acetylcholine, a neurotransmitter. Unlike standard treatments like beta-blockers or selective serotonin reuptake inhibitors (SSRIs), which mainly address symptoms like heart rate and anxiety, pyridostigmine targets the underlying autonomic dysfunction in POTS. Researchers are excited because this approach could offer more targeted relief with potentially fewer side effects, offering a promising alternative to conventional therapies.

What evidence suggests that pyridostigmine might be an effective treatment for POTS?

This trial will compare pyridostigmine with a placebo to evaluate its effectiveness for postural tachycardia syndrome (POTS). Research has shown that pyridostigmine can benefit people with POTS. In one study, 42% of patients reported improvement, increasing to 52% among those who tolerated the medication well. Pyridostigmine increases the activity of the part of the nervous system that helps control heart rate. Other studies have found it can lower the heart rate when standing by about 10%. This suggests pyridostigmine might help manage POTS symptoms by stabilizing heart rate and blood pressure. ^{2 3 6 7 8}

Who Is on the Research Team?

Wolfgang Singer, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Pyridostigmine

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

A 34-year-old woman diagnosed with postural orthostatic tachycardia syndrome (POTS) experienced significant symptoms like palpitations and dizziness when standing, which were confirmed through tilt table testing showing a heart rate increase of 55 beats/min without blood pressure changes.

After starting treatment with pyridostigmine, her symptoms improved significantly within four months, allowing her to return to her job as a nurse, demonstrating the efficacy of this medication for managing POTS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pyridostigmine in the treatment of postural orthostatic tachycardia syndrome]. Can, I., Tholakanahalli, V.[2018]

Pyridostigmine bromide has shown modest but statistically significant improvements in standing diastolic blood pressure and heart rate in patients with orthostatic intolerance, based on a review of 106 patients across multiple trials.

Despite some benefits, long-term data is insufficient to recommend routine use of pyridostigmine bromide for orthostatic intolerance, as 29% of patients discontinued therapy and the majority did not experience supine hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine in the treatment of orthostatic intolerance. Gales, BJ., Gales, MA.[2013]

A case of pyridostigmine toxicity was reported in a 47-year-old woman who ingested a high dose, leading to symptoms within an hour, but she recovered well after treatment with atropine and pralidoxime.

While pyridostigmine poisoning appears to be self-limiting and manageable in young adults, caution is advised for elderly patients due to potential severe cardiac effects, highlighting the need for prompt treatment in cases of overdose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine Suicidal Attempt in a Myasthenia Gravis Patient. Malabaey, MAT., Al-Saud, AA., Alaska, YA., et al.[2020]

In a study of 69 patients diagnosed with postural orthostatic tachycardia syndrome (POTS), 42% exhibited laboratory abnormalities indicating mast cell activation (MCA) disorder, particularly elevated levels of prostaglandins and histamine.

Many patients with POTS also reported additional nonorthostatic symptoms like migraines and gastrointestinal issues, suggesting that MCA disorder should be considered in their diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association. Kohno, R., Cannom, DS., Olshansky, B., et al.[2022]

Pyridostigmine has been shown to be a safe and effective treatment for a child with severe postural orthostatic tachycardia syndrome, demonstrating a favorable dose-dependent response over 9 months without major adverse effects.

The pharmacokinetic study revealed a short half-life of 2.29 hours, suggesting that a three-times-daily dosing schedule is optimal for maintaining therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of pyridostigmine in a child with postural tachycardia syndrome. Filler, G., Gow, RM., Nadarajah, R., et al.[2013]

In a study of 203 POTS patients treated with pyridostigmine over an average of 12 months, 51% of those who tolerated the medication experienced significant symptom relief, particularly in fatigue, palpitations, and presyncope.

Pyridostigmine treatment led to measurable improvements in orthostatic hemodynamic parameters, including a decrease in standing heart rate and an increase in standing diastolic blood pressure, although gastrointestinal issues were the most common side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. Kanjwal, K., Karabin, B., Sheikh, M., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21410722/

Pyridostigmine in the treatment of postural orthostatic ... The overall efficacy of pyridostigmine in our study was seen in 42% of total patients or 52% of patients who could tolerate taking the drug.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6095784/

Efficacy of Propranolol, Bisoprolol, and Pyridostigmine for ... Pyridostigmine, an acetylcholinesterase inhibitor widely prescribed to POTS patients, is considered to increase parasympathetic nervous system activity and ...

3. researchgate.net researchgate.net/publication/6519291_Pyridostigmine_in_the_Treatment_of_Orthostatic_Intolerance

Pyridostigmine in the Treatment of Orthostatic Intolerance When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly ...

4. semanticscholar.org semanticscholar.org/paper/Pyridostigmine-in-the-Treatment-of-Postural-A-Kanjwal-Karabin/7706fcfff320349629200ffbcc8058c4dd08b582

Pyridostigmine in the Treatment of Postural Orthostatic ... A retrospective, single‐center, long‐term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients ...

5. go.drugbank.com go.drugbank.com/drugs/DB00545

Pyridostigmine: Uses, Interactions, Mechanism of Action Pyridostigmine is the current drug of choice, with superior pharmacokinetics and reduced side effects compared to neostigmine. In addition to treating ...

6. drugs.com drugs.com/mestinon.html

Mestinon: Uses, Doses, Side Effects and More Clinical trials have used pyridostigmine to treat postural orthostatic tachycardia syndrome (POTS) but is not FDA approved for this condition.

7. drugs.com drugs.com/mtm/pyridostigmine.html

Pyridostigmine Uses, Side Effects & Warnings Mestinon (pyridostigmine) has been used to treat postural tachycardia syndrome (POTS) and may improve symptoms such as a fast heart rate ...

8. en.wikipedia.org en.wikipedia.org/wiki/Pyridostigmine

Pyridostigmine It is also used off-label to treat some forms of Postural orthostatic tachycardia syndrome. It is typically given by mouth but can also be used by injection.