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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 50 mg group | Active Comparator | Ten patients will receive 50 mg mirabegron for 8 weeks. |
|
| 25 mg group | Active Comparator | Ten patients will receive 25 mg mirabegron for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mirabegron 50 MG | Drug | 10 patients will receive drug for 8 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
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Inclusion Criteria:
Provision of signed and dated informed consent form.
Age > 18 years old.
Documented history of chronic (> 3 months) of orthostatic intolerance.
Diagnosis of syncope or pre-syncope and documented intermittent hypotension unresponsive to conventional life-style modification therapy.
Exclusion Criteria:
Patients with other potential etiologies of syncope
Heart failure with either preserved or reduced ejection fraction.
Wolff Parkinson-White Syndrome.
Stroke within the past 6 months.
Any history of myocardial infarction.
Active thyrotoxicosis.
Any experimental medication concomitantly or within 4 weeks of participation in the study.
Patients < 18 years old because mirabegron is not approved by FDA for use in children.
People with a history of allergy to ECG electrodes or adhesive tape.
Patients with known contraindications or precautions to mirabegron.
Prisoners
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 50 mg Group | Ten patients will receive 50 mg mirabegron for 8 weeks. Mirabegron 50 MG: 10 patients will receive drug for 8 weeks |
| FG001 | 25 mg Group | Ten patients will receive 25 mg mirabegron for 8 weeks. Mirabegron 25 MG: 10 patients will receive drug for 8 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 50 mg Group | Ten patients will receive 50 mg mirabegron for 8 weeks. Mirabegron 50 MG: 10 patients will receive drug for 8 weeks |
| BG001 | 25 mg Group | Ten patients will receive 25 mg mirabegron for 8 weeks. Mirabegron 25 MG: 10 patients will receive drug for 8 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Out of 10 participants, only 7 participants in the 50 mg group and 8 participants in the 25 mg group had ABPM available for comparison at both baseline and at 8 weeks. Therefore, we only included them in the analysis to determine if there are significant changes of blood pressure from baseline to 8 weeks. Patients with incomplete data were not analyzed because we cannot compare baseline with 8 weeks. | Posted | Mean | Standard Deviation | mmHg | 8 weeks |
|
8 Weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 50 mg Group | Ten patients will receive 50 mg mirabegron for 8 weeks. Mirabegron 50 MG: 10 patients will receive drug for 8 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peng-Sheng Chen, MD | Cedars-Sinai Medical Center | 310-967-2707 | Peng-Sheng.Chen@cshs.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 12, 2024 | Sep 29, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 27, 2024 | Sep 29, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D054972 | Postural Orthostatic Tachycardia Syndrome |
| D013575 | Syncope |
| ID | Term |
|---|---|
| D054971 | Orthostatic Intolerance |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C520025 | mirabegron |
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All patients will receive mirabegron 50 mg or 25 mg orally for 8 weeks to determine their effects on blood pressure.
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| Mirabegron 25 MG | Drug | 10 patients will receive drug for 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. |
| 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. | 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. | 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. | 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 | 8 weeks |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Medications | Medications being taken and number of participants in each group taking them. | Number | participants |
|
| Diagnoses | Diagnoses of participants and number of participants with the diagnosis. | Number | participants |
|
| Average Sinus Rate | Mean | Standard Deviation | beats per minute |
|
| OG001 | 25 mg Group | Ten patients will receive 25 mg mirabegron for 8 weeks. Mirabegron 25 MG: 10 patients will receive drug for 8 weeks |
|
|
| Secondary | 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. | 2 participants in each group did not complete follow-up assessments at week 8. Therefore, only 8 participants in each group were analyzed at all timepoints. | Posted | Mean | Standard Deviation | average number of episodes | 8 weeks |
|
|
|
| Secondary | 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. | 2 participants in each group exited the study early. An additional participant in the 50 mg group did not complete ABPM at Week 8. Therefore, we analyzed the remaining 7 participants in the 50 mg group and 8 participants in the 25 mg group for all timepoints. The patients with incomplete data were excluded from the analysis. | Posted | Mean | Standard Deviation | average number of episodes | 8 weeks |
|
|
|
| Secondary | 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. | The purpose was to compare the scores between baseline and 8 weeks. Eight participants in each group had both baseline and 8 weeks data. They were analyzed. Two participants in each group exited the study early and were excluded from the analysis due to incomplete data. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| Secondary | 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. | The purpose was to compare the scores between baseline and 8 weeks. Eight participants in each group had both baseline and 8 weeks data. They were analyzed. Two participants in each group exited the study early and were excluded from the analysis due to incomplete data. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| Secondary | 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. | The purpose was to compare the scores between baseline and 8 weeks. Eight participants in each group had both baseline and 8 weeks data. They were analyzed. Two participants in each group exited the study early and were excluded from the analysis due to incomplete data. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| Secondary | 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 | The purpose was to compare the scores between baseline and 8 weeks. Eight participants in each group had both baseline and 8 weeks data. They were analyzed. Two participants in each group exited the study early and were excluded from the analysis due to incomplete data. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 5 |
| 10 |
| EG001 | 25 mg Group | Ten patients will receive 25 mg mirabegron for 8 weeks. Mirabegron 25 MG: 10 patients will receive drug for 8 weeks | 0 | 10 | 0 | 10 | 5 | 10 |
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Urinary Discomfort | Renal and urinary disorders | Non-systematic Assessment |
|
| Blurry Vision | Eye disorders | Non-systematic Assessment |
|
| Skin Irritation from Patch Electrode | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Palpitations | Nervous system disorders | Non-systematic Assessment |
|
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| D014474 | Unconsciousness |
| D003244 | Consciousness Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Calculated Score-Week 8 |
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| Your Health Today Score-Week 8 |
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| Angina Frequency-Week 0 |
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| Treatment Satisfaction-Week 0 |
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| QOL-Week 0 |
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| Summary-Week 0 |
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| Physical Limitation-Week 8 |
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| Angina Stability-Week 8 |
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| Angina Frequency-Week 8 |
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| Treatment Satisfaction-Week 8 |
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| QOL-Week 8 |
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| Summary-Week 8 |
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| Severity Score-Week 8 |
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| HRQoL Score-Week 8 |
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