Using Mirabegron to Increase BP in Patients With POTS (RAISE-BP)

Using Mirabegron to Increase Blood Pressure in Patients With Postural Orthostatic Tachycardia Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Syncope; Postural Orthostatic Tachycardia Syndrome; Chronic Orthostatic Intolerance
• Intervention / Treatment: Drug: Mirabegron 50 MG; Drug: Mirabegron 25 MG

Detailed Description

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 investigators will perform 24-hour ambulatory blood pressure monitoring (ABPM) and ambulatory skin sympathetic nerve activity (SKNA) recording using a Bittium Faros electrocardiogram (ECG) monitor, assess the number of syncope and presyncope episodes and determine the symptoms using validated questionnaires at baseline. The patients will then be given mirabegron (either 25 mg once daily or 50 mg once daily) for eight weeks. Afterward, the patient will return to the clinic for clinical assessments, complete questionnaires, ABPM, and ambulatory SKNA recording while still on treatment. Mirabegron will be stopped when the data collection is complete. Because mirabegron has a long half-life, the investigators will schedule a video visit with the patient 12 weeks after beginning the treatment and inquire about the patient's symptoms. The investigators will repeat all pertinent questionnaires at that time.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Age > 18 years old.
3. Documented history of chronic (> 3 months) of orthostatic intolerance.

4. Diagnosis of syncope or pre-syncope and documented intermittent hypotension unresponsive to conventional life-style modification therapy.

   1. A history of syncope (complete loss of consciousness) or presyncope (the sensation that one is about to pass out).
   2. At least one documented hypotensive episode with systolic BP < 90 mmHg on 24-hr ABPM.
   3. Inadequate response to conventional therapies.

Exclusion Criteria:

1. Patients with other potential etiologies of syncope

   1. Sustained tachyarrhythmias other than sinus tachycardia. Specifically, patients with a diagnosis of atrial fibrillation, sustained (> 30 seconds) arrhythmias including paroxysmal supraventricular tachycardia, atrial flutter, ventricular tachycardia, ventricular fibrillation.
   2. Symptomatic bradycardia before pacemaker implantation.
2. Heart failure with either preserved or reduced ejection fraction.
3. Wolff Parkinson-White Syndrome.
4. Stroke within the past 6 months.
5. Any history of myocardial infarction.
6. Active thyrotoxicosis.
7. Any experimental medication concomitantly or within 4 weeks of participation in the study.
8. Patients < 18 years old because mirabegron is not approved by FDA for use in children.
9. People with a history of allergy to ECG electrodes or adhesive tape.

10. Patients with known contraindications or precautions to mirabegron.

    1. Hypertension
    2. Severe renal impairment (calculated CrCl < 30ml/min)
    3. Hepatic disease (Child-Pugh Class B)
    4. Pregnant or lactation
    5. Geriatric patients in long term care facilities
    6. Patients who are known to be allergic to mirabegron
    7. Patients taking drugs that are CYP2D6 substrates, such as midodrine. An extensive list can be found at the following website: https://drug-interactions.medicine.iu.edu/MainTable.aspx
11. Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 50 mg group; Ten patients will receive 50 mg mirabegron for 8 weeks.	Drug: Mirabegron 50 MG; 10 patients will receive drug for 8 weeks; Other Names: Myrbetriq
Active Comparator: 25 mg group; Ten patients will receive 25 mg mirabegron for 8 weeks.	Drug: Mirabegron 25 MG; 10 patients will receive drug for 8 weeks; Other Names: Myrbetriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	A 24-hr ambulatory blood pressure monitor (ABPM) was used to measure systolic blood pressure (SBP) and diastolic blood pressure (DBP). The participants' average SBP is the primary outcome. We also report the average DBP in this Table. Due to technical reasons, only 7 participants in 50 mg group and 8 participants in 25 mg group had ABPM available for analysis.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Syncope	Change of frequencies of syncope and presyncope. Two of the initial 10 participants of each group exited the study early. So that we can compare the frequency of syncope at baseline with that at 8 weeks, we excluded those two patients from analysis. Therefore, we analyzed the 8 remaining participants in each group.	8 weeks
Hypotensive Episode	Change of the hypotensive (systolic BP < 90 mmHg) episodes during wake time using ABPM, which is available in 7 participants in the 50 mg group and 8 in the 25 mg group. They were used to compare between baseline and 8 weeks. Patients without complete data were excluded from analysis.	8 weeks
Duke Activity Status Index Questionnaire	Change of functional capacity score as measured by the Duke Activity Status index questionnaire. DASI (The Duke Activity Status Index): 0 to 58.2. The higher the score, the greater the individual's functional capacity.	8 weeks
EQ-5D-5L Questionnaire	EuroQol 5-Dimension 5-Level, a questionnaire used to measure health-related quality of life across five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) with five response levels each, designed to be more sensitive than earlier versions. The 5-component scale includes mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. EQ-5D-5L: calculated score best = 1, worst = -0.573; EQ-5D-5L YHT (Your Health Today) score is self-reported by the patient on a 0-100 scale, with 100 being the best.	8 weeks
Seattle Angina Questionnaire (SAQ)	Change of QOL and symptoms of angina as measured by the SAQ based on five scales: physical limitation scale, anginal stability scale, anginal frequency scale, treatment satisfaction scale, and the disease perception scale. Seattle Angina Questionnaire score on a 0-100 scale, with 100 being the best. SAQ subscales (physical limitation scale, anginal stability scale, anginal frequency scale, treatment satisfaction scale, and the disease perception scale) all have a 0-100 scale, with 100 being the best. A total SAQ score can be calculated by averaging all domain scores.	8 weeks
Overactive Bladder Symptoms	Overactive Bladder Questionnaire Short Form (OAB-q SF) measures change in Overactive Bladder (OAB) symptoms. The severity score: best = 0, worst = 100. OAB-Q SF Health-Related quality of life (HRQoL) assessments evaluate the impact of OAB symptoms on a patient's quality of life. HRQoL best = 100, worst = 0	8 weeks

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2023
• Primary Completion (Actual): May 20, 2025
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 9, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Consciousness Disorders; Unconsciousness; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Syncope; Postural Orthostatic Tachycardia Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic Agonists; Adrenergic Agents; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Urological Agents; mirabegron
• Other Study ID Numbers: STUDY00002281

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No