Mirabegron for Postural Orthostatic Tachycardia Syndrome

(RAISE BP Trial)

Overseen By Anxhela Kote, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cedars-Sinai Medical Center

Must not be taking: CYP2D6 substrates

Disqualifiers: Heart failure, Stroke, Myocardial infarction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mirabegron, a medication, to determine if it can alleviate symptoms in people with postural orthostatic tachycardia syndrome (POTS). POTS can cause dizziness or fainting when standing due to low blood pressure. Researchers aim to discover if mirabegron can increase blood pressure, reduce fainting, and improve overall well-being. The trial seeks individuals who have experienced frequent dizziness or fainting for over three months, despite trying other treatments. Participants will receive either 25 mg or 50 mg of mirabegron for eight weeks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking any experimental medications within 4 weeks of participation and any drugs that are CYP2D6 substrates, like midodrine. If you're on these medications, you may need to stop them before joining the trial.

Is there any evidence suggesting that mirabegron is likely to be safe for humans?

Research has shown that mirabegron has been used safely in various studies. For individuals with overactive bladder (OAB), studies have found that mirabegron is generally well-tolerated, with no major safety differences between younger and older adults, suggesting it is safe for many people.

In one study on postural orthostatic tachycardia syndrome (POTS), 20% of patients experienced a specific change in heart activity, but this doesn't necessarily indicate it is unsafe. The FDA has already approved mirabegron for treating OAB, which supports its safety. However, since this trial is in an early phase, researchers are still determining the best and safest doses for POTS.

Overall, while some side effects exist, studies have shown that mirabegron is generally well-tolerated. Participants might experience mild effects, but serious issues are rare. ^{1 2 3 4 5}

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

Most treatments for Postural Orthostatic Tachycardia Syndrome (POTS) focus on managing symptoms through lifestyle changes and medications like beta-blockers or fludrocortisone. But mirabegron works differently, targeting the beta-3 adrenergic receptors to improve blood flow and potentially reduce heart rate abnormalities. Researchers are excited about mirabegron because it offers a novel mechanism of action that could provide relief for POTS patients who don't respond well to current options. Additionally, the trial explores two different doses, 25 mg and 50 mg, to find the most effective and safe dosage, offering hope for personalized treatment.

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

Research has shown that mirabegron might help raise blood pressure in people with postural orthostatic tachycardia syndrome (POTS). In studies, some patients experienced better blood pressure control and fewer instances of fainting or feeling faint. Mirabegron is already used to treat overactive bladder (OAB), a symptom being examined in POTS patients. Although limited data exists on its effectiveness for POTS, its ability to improve blood pressure and bladder issues suggests potential benefits for this condition. Participants in this trial will receive either 25 mg or 50 mg of mirabegron to evaluate its effectiveness for POTS. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Postural Orthostatic Tachycardia Syndrome (POTS) who often feel faint or have rapid heartbeats due to low blood pressure and haven't found relief with standard treatments. It's not for those allergic to Mirabegron, pregnant, breastfeeding, with severe kidney issues, certain heart conditions, recent stroke or heart attack, active thyroid problems, or taking specific drugs.

Inclusion Criteria

I have fainting spells or near-fainting due to low blood pressure not improved by lifestyle changes.

I have a history of fainting or almost fainting.

I have had symptoms when standing for more than 3 months.

Exclusion Criteria

I have a fast heart rate that is not due to sinus tachycardia.

I experienced slow heartbeats before getting a pacemaker.

I cannot take mirabegron due to health risks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirabegron (either 25 mg or 50 mg) for 8 weeks to assess its effects on blood pressure, syncope, and other symptoms

8 weeks

1 visit (in-person) at baseline, 1 visit (in-person) after 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a video visit 12 weeks after starting treatment

4 weeks

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron

Trial Overview The study tests if Mirabegron can help raise blood pressure and improve life quality in POTS patients by preventing fainting spells and reducing chest pain and bladder symptoms. Two doses of Mirabegron (25 MG & 50 MG) are being compared to find the most effective one.

How Is the Trial Designed?

Group I: 25 mg group Active Control 1 Intervention

Ten patients will receive 25 mg mirabegron for 8 weeks.

Group II: 50 mg group Active Control 1 Intervention

Ten patients will receive 50 mg mirabegron for 8 weeks.

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

Approved in United States as Myrbetriq for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in European Union as Mirabegron for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Published Research Related to This Trial

In a retrospective case series of 20 POTS patients treated with ivabradine, 60% reported symptomatic improvement, particularly in tachycardia and fatigue, suggesting potential efficacy for this treatment.

Despite the positive outcomes, some patients discontinued ivabradine due to lack of efficacy or side effects, highlighting the need for further randomized controlled trials to better assess its effectiveness in POTS patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. McDonald, C., Frith, J., Newton, JL.[2021]

In a study of 20 patients with postural orthostatic tachycardia syndrome (POTS), 20% showed significantly decreased myocardial uptake of MIBG, indicating potential cardiac sympathetic nerve damage.

The findings suggest that POTS may involve autonomic cardiac neuropathy, and MIBG myocardial scintigraphy could help differentiate neuropathic POTS from other types of orthostatic intolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac neurotransmission imaging with 123I-meta-iodobenzylguanidine in postural tachycardia syndrome. Haensch, CA., Lerch, H., Schlemmer, H., et al.[2017]

Ivabradine, a medication that selectively inhibits the If ion current in the sinoatrial node, has shown promise in treating a case of Postural Orthostatic Tachycardia Syndrome (POTS), which is characterized by an inappropriate increase in heart rate upon standing.

POTS is a complex condition often linked to autonomic dysfunction and elevated norepinephrine levels, and while beta blockers have been used for treatment, this case suggests that Ivabradine may be an effective alternative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Ivabradine in Postural Orthostatic Tachycardia Syndrome. Jamil-Copley, S., Nagarajan, DV., Baig, MK.[2020]

A 44-year-old woman with postural orthostatic tachycardia syndrome (POTS) experienced successful heart rate reduction using ivabradine, a medication that targets the sinus node, after traditional treatments failed.

Following treatment with ivabradine, the patient showed no signs of POTS on follow-up tests and reported significant symptom improvement, suggesting that ivabradine may be a beneficial option for patients with resistant inappropriate sinus tachycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of inappropriate sinus tachycardia with ivabradine in a patient with postural orthostatic tachycardia syndrome and a dual chamber pacemaker. Khan, S., Hamid, S., Rinaldi, C.[2018]

In a study of 27 children with postural orthostatic tachycardia syndrome, ivabradine led to symptom improvement in 67% of patients, particularly reducing syncope/presyncope by 90%.

Ivabradine significantly lowered heart rates in both sitting and standing positions without causing significant changes in blood pressure, although some patients experienced mild side effects like visual disturbances and bradycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivabradine in children with postural orthostatic tachycardia syndrome: a retrospective study. Towheed, A., Nesheiwat, Z., Mangi, MA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06133075

Using Mirabegron to Increase BP in Patients With POTS This is a pilot dose-finding study to test the hypothesis that mirabegron increases systolic blood pressure (BP), prevents syncope/presyncope, and improves the ...

2. withpower.com withpower.com/trial/phase-2-orthostatic-intolerance-10-2023-cba04

Mirabegron for Postural Orthostatic Tachycardia Syndrome In a study of 20 patients with postural orthostatic tachycardia syndrome (POTS), 20% showed significantly decreased myocardial uptake of MIBG, indicating ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06133075/using-mirabegron-to-increase-bp-in-patients-with-pots

Using Mirabegron to Increase BP in Patients With POTS This is a pilot dose-finding study to test the hypothesis that mirabegron increases systolic blood pressure (BP), prevents syncope/presyncope, and improves the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02757768

NCT02757768 | A Study to Evaluate the Efficacy, Safety, ... The purpose of the study was to assess the efficacy, safety, and tolerability of mirabegron versus placebo in men with overactive bladder (OAB) symptoms ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3491758/

Mirabegron: a review of recent data and its prospects in the ... Treatment with the to-be-marketed dose of 50 mg achieved the primary efficacy objectives, although it resulted only in a reduction of 0.55 micturitions per 24 h ...

6. myrbetriqhcp.com myrbetriqhcp.com/safety/

Safety | MYRBETRIQ® (mirabegron ER tablets) No overall differences in safety or effectiveness were observed between patients <65 years and those ≥65 years of age in the Phase II and III studies of ...