Postural Orthostatic Tachycardia Syndrome, Chronic Orthostatic Intolerance, Syncope
Conditions
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.
Interventions
DRUGMirabegron 50 MG
10 patients will receive drug for 8 weeks
DRUGMirabegron 25 MG
10 patients will receive drug for 8 weeks
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients will receive mirabegron 50 mg or 25 mg orally for 8 weeks to determine their effects on blood pressure.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | 8 weeks | Mirabegron changes the average systolic BP in 24-hr ABPM recording |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypotensive episode | 8 weeks | Change of the hypotensive (systolic BP \< 90 mmHg) episodes during wake time using ABPM |
| Duke Activity Status Index Questionnaire | 8 weeks | Change of functional capacity score as measured by the Duke Activity Status index questionnaire |
| Syncope | 8 weeks | Change of frequencies of syncope and presyncope |
| Seattle Angina Questionnaire (SAQ) | 8 weeks | 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. |
| Overactive Bladder symptoms | 8 weeks | Change in OAB symptoms as measured by the OAB-q SF |
| EQ-5D-5L Questionnaire | 8 weeks | Change of health related QOL score using a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression |
Countries
United States
Outcome results
None listed