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: Recruiting
• 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 (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anxhela Kote, BS; Phone Number: 310-967-3854; Email: anxhela.kote@cshs.org
• Study Contact Backup: Name: Peng-Sheng Chen, MD; Phone Number: 310-967-2707; Email: chenp3@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Anxhela Kote, BS; Phone Number: 310-967-3854; Email: anxhela.kote@cshs.org
      • Principal Investigator: Peng-Sheng Chen, MD

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	Mirabegron changes the average systolic BP in 24-hr ABPM recording	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Syncope	Change of frequencies of syncope and presyncope	8 weeks
Hypotensive episode	Change of the hypotensive (systolic BP < 90 mmHg) episodes during wake time using ABPM	8 weeks
Duke Activity Status Index Questionnaire	Change of functional capacity score as measured by the Duke Activity Status index questionnaire	8 weeks
EQ-5D-5L Questionnaire	Change of health related QOL score using a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression	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.	8 weeks
Overactive Bladder symptoms	Change in OAB symptoms as measured by the OAB-q SF	8 weeks

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2023
• Primary Completion (Estimated): November 21, 2025
• Study Completion (Estimated): November 21, 2026

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 (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Syndrome; Tachycardia; Syncope; Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; 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