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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Syncope | 8 weeks | 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. |
| Hypotensive Episode | 8 weeks | 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. |
| Duke Activity Status Index Questionnaire | 8 weeks | 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. |
| EQ-5D-5L Questionnaire | 8 weeks | 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. |
| 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. 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. |
| Overactive Bladder Symptoms | 8 weeks | 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 |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 13 |
| Average Sinus Rate | 69 beats per minute STANDARD_DEVIATION 8 |
| Diagnoses Alcohol Sensitive | 1 participants |
| Diagnoses Chest Pain | 4 participants |
| Diagnoses Dizziness | 7 participants |
| Diagnoses Hyperadrenergic POTS | 5 participants |
| Diagnoses Hypermobile Ehlers-Danlos Syndrome (hEDs) | 6 participants |
| Diagnoses Mast Cell Activation Syndrome (MCAS) | 6 participants |
| Diagnoses Mitral Valve Prolapse | 1 participants |
| Diagnoses Palpitations | 6 participants |
| Diagnoses Paroxysmal Supraventricular Tachycardia (pSVT) | 0 participants |
| Diagnoses Post-Prandial Hypotension | 0 participants |
| Diagnoses Pre-Syncope | 9 participants |
| Diagnoses Skin Sensitivity | 10 participants |
| Diagnoses Syncope | 3 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Medications Atenolol | 1 participants |
| Medications Bisoprolol | 0 participants |
| Medications Citalopram | 0 participants |
| Medications Cromolyn Sodium | 2 participants |
| Medications Diphenhydramine | 1 participants |
| Medications Famotidine | 5 participants |
| Medications Fludrocortisone | 3 participants |
| Medications Ivabradine | 4 participants |
| Medications Midodrine | 2 participants |
| Medications Naloxone | 0 participants |
| Medications Verapamil | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 5 / 10 | 5 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
None listed