Clinical trial NCT06133075: Using Mirabegron to Increase BP in Patients With POTS
Official title: Using Mirabegron to Increase Blood Pressure in Patients With Postural Orthostatic Tachycardia Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Postural Orthostatic Tachycardia Syndrome
Chronic Orthostatic Intolerance
Syncope
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2023-11-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All patients will receive mirabegron 50 mg or 25 mg orally for 8 weeks to determine their effects on blood pressure.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood Pressure
timeFrame: 8 weeks
Secondary outcomes:
measure: Syncope
timeFrame: 8 weeks
measure: Hypotensive episode
timeFrame: 8 weeks
measure: Duke Activity Status Index Questionnaire
timeFrame: 8 weeks
measure: EQ-5D-5L Questionnaire
timeFrame: 8 weeks
measure: Seattle Angina Questionnaire (SAQ)
timeFrame: 8 weeks
measure: Overactive Bladder symptoms
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
References: