Ignite Creation Date:
2024-05-06 @ 1:59 PM
Last Modification Date:
2024-10-26 @ 1:23 PM
Study NCT ID:
NCT04186286
Status:
RECRUITING
Last Update Posted:
2024-05-09
First Post:
2019-11-21
Brief Title:
Crossover Study of Propranolol vs Ivabradine in POTS
Sponsor:
University of Calgary
Organization:
University of Calgary
Study Overview
Official Title:
A Randomized Crossover Study of Propranolol Versus Ivabradine in Postural Tachycardia Syndrome POTS
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
10 BACKGROUND Postural tachycardia syndrome POTS is a disorder of chronic orthostatic intolerance characterized by symptoms of palpitations lightheadedness chest discomfort shortness of breath blurred vision and mental clouding These symptoms occur during standing and are associated with a marked increase in heart rate HR in the absence of hypotension which typically resolve when sitting or lying down Most importantly POTS is associated with a very poor quality of life and significant functional disability POTS patients commonly experience mental clouding brain fog even while lying down or seated which poses significant limitations to daily activities
Unfortunately there is a relative paucity in the literature assessing therapies for POTS patients Given that excessive tachycardia on standing is a fundamental component of this syndrome a handful of studies have evaluated medications that reduce HR Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions
20 RATIONALE STUDY PURPOSE The investigators propose to compare the efficacy of propranolol and ivabradine on HR response to standing and symptom burden in patients with POTS
30 Study Design This will be a single-center double-blind placebo-controlled randomized crossover trial conducted in patients with POTS to compare effects of 1 oral ivabradine 5 mg bid plus placebo BID to fill out a QID schedule 2 oral propranolol 10 mg qid and 3 oral placebo qid in POTS patients After a baseline screening assessment following a washout period of 7 days participants will be randomized to start with a 4-week course of either ivabradine propranolol or placebo The other two treatments will be given in separate 4-week courses with a 7-day washout period between phases with each participant acting as his or her own control At the end of each 4-week phase participants will complete the symptom-rating and HRQOL questionnaires and also undergo tilt table testing to assess the change in HR at 10 min with head up tilt
Participants will undergo POTS testing at baseline and at the end of each 4-week treatment course This will involve a total of 4 separate study visits
Unfortunately there is a relative paucity in the literature assessing therapies for POTS patients Given that excessive tachycardia on standing is a fundamental component of this syndrome a handful of studies have evaluated medications that reduce HR Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions
20 RATIONALE STUDY PURPOSE The investigators propose to compare the efficacy of propranolol and ivabradine on HR response to standing and symptom burden in patients with POTS
30 Study Design This will be a single-center double-blind placebo-controlled randomized crossover trial conducted in patients with POTS to compare effects of 1 oral ivabradine 5 mg bid plus placebo BID to fill out a QID schedule 2 oral propranolol 10 mg qid and 3 oral placebo qid in POTS patients After a baseline screening assessment following a washout period of 7 days participants will be randomized to start with a 4-week course of either ivabradine propranolol or placebo The other two treatments will be given in separate 4-week courses with a 7-day washout period between phases with each participant acting as his or her own control At the end of each 4-week phase participants will complete the symptom-rating and HRQOL questionnaires and also undergo tilt table testing to assess the change in HR at 10 min with head up tilt
Participants will undergo POTS testing at baseline and at the end of each 4-week treatment course This will involve a total of 4 separate study visits
Detailed Description:
10 BACKGROUND Postural tachycardia syndrome POTS is a disorder of chronic orthostatic intolerance characterized by symptoms of palpitations lightheadedness chest discomfort shortness of breath blurred vision and mental clouding These symptoms occur during standing and are associated with a marked increase in heart rate HR in the absence of hypotension which typically resolve when sitting or lying down Most importantly POTS is associated with a very poor quality of life and significant functional disability POTS patients commonly experience mental clouding brain fog even while lying down or seated which poses significant limitations to daily activities
Unfortunately there is a relative paucity in the literature assessing therapies for POTS patients Given that excessive tachycardia on standing is a fundamental component of this syndrome a handful of studies have evaluated medications that reduce HR In a randomized crossover study of 54 patients with POTS low-dose propranolol 10-20 mg PO was found to acutely reduce standing HR compared to placebo Further there was greater improvement in symptom burden quantified using the Vanderbilt Orthostatic Symptom Score VOSS from baseline to 2 hours in patients treated with propranolol compared to placebo
Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions In non-randomized reports it has been shown to improve symptoms in patients with POTS In a case series of 22 patients approximately 60 of patients with POTS treated with ivabradine had symptom improvement
20 RATIONALE STUDY PURPOSE Patients with POTS suffer great disability and currently used pharmacologic therapies require more rigorous study Currently there are no studies comparing the relative efficacy of propranolol and ivabradine in patients with POTS
We propose to compare the efficacy of propranolol and ivabradine on HR response to standing and symptom burden in patients with POTS This would be the first study to compare the relative efficacy of ivabradine to propranolol in POTS The results of this exploratory study may help inform design of a larger multicenter clinical trial investigating the use of ivabradine or propranolol in POTS over time We will test the null hypothesis that the heart rate lowering response to ivabradine is not different than the heart lowering response of propranolol
In addition we propose to assess sleep complaints and sleep quality using questionnaire and actigraphy based assessments
30 Study Design This will be a multi-center double-blind placebo-controlled randomized crossover trial conducted in patients with POTS to compare effects of 1 oral ivabradine 5 mg bid plus placebo BID to fill out a QID schedule 2 oral propranolol 10 mg qid and 3 oral placebo qid in POTS patients After a baseline screening assessment following a washout period of 7 days participants will be randomized to start with a 4-week course of either ivabradine propranolol or placebo The other two treatments will be given in separate 4-week courses with a 7-day washout period between phases with each participant acting as his or her own control At the end of each 4-week phase participants will complete the symptom-rating and HRQOL questionnaires and also undergo tilt table testing to assess the change in HR at 10 min with head up tilt
Participants will undergo POTS testing at baseline and at the end of each 4-week treatment course in the Libin Cardiovascular Institute TRW Human Physiology Research space This will involve a total of 4 separate study visits
Studies will start between 8-9am with the patient in a fasting state to avoid acute hemodynamic effects from eating
Prior to hemodynamic data collection a brief medical history will be conducted to ensure that the medications have not changed and that there are not new medical issues that would make the study unsafe or imprudent
Participants will be instrumented for continuous beat-to-beat BP and electrocardiographic monitoring BP will be monitored continuously using a finger volume clamp method Nexfin BMEYE Inc and calibrated with intermittent brachial cuff measurements using a standard automatic BP monitor IVY Model 450C IVY Medical Branford CT USA or by using Finapres NOVA Finapres Medical Systems
Baseline seated continuous data EKG signals and continuous BP will be collected for 10 min
Neuropsychological testing of the cognitive domains of memory attention and executive function will be assessed using the Cambridge Neuropsychological Test Automated Battery CANTAB while seated
The patient will be asked to stand and repeat portions of the CANTAB tests
Baseline lying down continuous data EKG signals and continuous BP will be collected for 10 min
The patient will then be strapped onto the tilt table and then tilted to 80 head-up for 10 minutes with continuous hemodynamic data collection Oxygen saturation will be assessed from a finger probe End-tidal CO2 will be measured using nasal prongs
Participants will be asked to comment on any side effects or unrated symptoms
VOSS ratings will be collected at the end of tilt
Participants and the research staff will be asked to guess at which intervention was given on that study day not applicable to baseline visit
After the study is finished we will remove the recording patches and electrodes This testing day will last about 3 hours
Upon conclusion of the tilt testing we will connect patients to a 24-hour Holter monitor for continuous ECG and HR monitoring Participants will return the monitoring device the following day
This testing protocol will be repeated at baseline and at the end of phase 1 2 and 3 with different study drugs
Unfortunately there is a relative paucity in the literature assessing therapies for POTS patients Given that excessive tachycardia on standing is a fundamental component of this syndrome a handful of studies have evaluated medications that reduce HR In a randomized crossover study of 54 patients with POTS low-dose propranolol 10-20 mg PO was found to acutely reduce standing HR compared to placebo Further there was greater improvement in symptom burden quantified using the Vanderbilt Orthostatic Symptom Score VOSS from baseline to 2 hours in patients treated with propranolol compared to placebo
Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions In non-randomized reports it has been shown to improve symptoms in patients with POTS In a case series of 22 patients approximately 60 of patients with POTS treated with ivabradine had symptom improvement
20 RATIONALE STUDY PURPOSE Patients with POTS suffer great disability and currently used pharmacologic therapies require more rigorous study Currently there are no studies comparing the relative efficacy of propranolol and ivabradine in patients with POTS
We propose to compare the efficacy of propranolol and ivabradine on HR response to standing and symptom burden in patients with POTS This would be the first study to compare the relative efficacy of ivabradine to propranolol in POTS The results of this exploratory study may help inform design of a larger multicenter clinical trial investigating the use of ivabradine or propranolol in POTS over time We will test the null hypothesis that the heart rate lowering response to ivabradine is not different than the heart lowering response of propranolol
In addition we propose to assess sleep complaints and sleep quality using questionnaire and actigraphy based assessments
30 Study Design This will be a multi-center double-blind placebo-controlled randomized crossover trial conducted in patients with POTS to compare effects of 1 oral ivabradine 5 mg bid plus placebo BID to fill out a QID schedule 2 oral propranolol 10 mg qid and 3 oral placebo qid in POTS patients After a baseline screening assessment following a washout period of 7 days participants will be randomized to start with a 4-week course of either ivabradine propranolol or placebo The other two treatments will be given in separate 4-week courses with a 7-day washout period between phases with each participant acting as his or her own control At the end of each 4-week phase participants will complete the symptom-rating and HRQOL questionnaires and also undergo tilt table testing to assess the change in HR at 10 min with head up tilt
Participants will undergo POTS testing at baseline and at the end of each 4-week treatment course in the Libin Cardiovascular Institute TRW Human Physiology Research space This will involve a total of 4 separate study visits
Studies will start between 8-9am with the patient in a fasting state to avoid acute hemodynamic effects from eating
Prior to hemodynamic data collection a brief medical history will be conducted to ensure that the medications have not changed and that there are not new medical issues that would make the study unsafe or imprudent
Participants will be instrumented for continuous beat-to-beat BP and electrocardiographic monitoring BP will be monitored continuously using a finger volume clamp method Nexfin BMEYE Inc and calibrated with intermittent brachial cuff measurements using a standard automatic BP monitor IVY Model 450C IVY Medical Branford CT USA or by using Finapres NOVA Finapres Medical Systems
Baseline seated continuous data EKG signals and continuous BP will be collected for 10 min
Neuropsychological testing of the cognitive domains of memory attention and executive function will be assessed using the Cambridge Neuropsychological Test Automated Battery CANTAB while seated
The patient will be asked to stand and repeat portions of the CANTAB tests
Baseline lying down continuous data EKG signals and continuous BP will be collected for 10 min
The patient will then be strapped onto the tilt table and then tilted to 80 head-up for 10 minutes with continuous hemodynamic data collection Oxygen saturation will be assessed from a finger probe End-tidal CO2 will be measured using nasal prongs
Participants will be asked to comment on any side effects or unrated symptoms
VOSS ratings will be collected at the end of tilt
Participants and the research staff will be asked to guess at which intervention was given on that study day not applicable to baseline visit
After the study is finished we will remove the recording patches and electrodes This testing day will last about 3 hours
Upon conclusion of the tilt testing we will connect patients to a 24-hour Holter monitor for continuous ECG and HR monitoring Participants will return the monitoring device the following day
This testing protocol will be repeated at baseline and at the end of phase 1 2 and 3 with different study drugs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None