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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
10 patients will receive drug for 8 weeks
10 patients will receive drug for 8 weeks
Cedars-Sinai Medical Center
Los Angeles, California, United States
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.
Time frame: 8 weeks
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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Time frame: 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.
Time frame: 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
Time frame: 8 weeks