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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a pilot dose-finding study to test the hypothesis that mirabegron increases systolic blood pressure (BP), prevents syncope/presyncope, and improves the quality of life (QOL), functional capacity, chest pain, and overactive bladder (OAB) symptoms in patients with postural orthostatic tachycardia syndrome (POTS) who have a documented history of hypotension inadequately responsive to conventional treatments. The American Heart Association funds this study.

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.

How does the drug Mirabegron differ from other drugs for treating Postural Orthostatic Tachycardia Syndrome (POTS)?

Mirabegron is unique because it is primarily used to treat overactive bladder by relaxing the bladder muscle, whereas other drugs for POTS, like Ivabradine, work by directly affecting heart rate. This novel approach may offer a different mechanism of action for managing POTS symptoms. ^{1 2 3 4 5}

Eligibility Criteria

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 am 18 years old or older.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cardiac neurotransmission imaging with 123I-meta-iodobenzylguanidine in postural tachycardia syndrome. [2017]

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

Use of Ivabradine in Postural Orthostatic Tachycardia Syndrome. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Ivabradine in children with postural orthostatic tachycardia syndrome: a retrospective study. [2021]

5. United States 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. [2018]