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 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 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. ^{1 2 3 4 5}

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. ^{1 2 3 4 5}

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. ^{1 2 3 5 6}

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

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]

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]

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]

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]

Citations

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

Pharmacokinetics of pyridostigmine in a child with postural tachycardia syndrome. [2013]

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

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. [2013]

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

[Pyridostigmine in the treatment of postural orthostatic tachycardia syndrome]. [2018]

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

Pyridostigmine in the treatment of orthostatic intolerance. [2013]

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

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association. [2022]

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

Pyridostigmine Suicidal Attempt in a Myasthenia Gravis Patient. [2020]