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Crossover Study of Propranolol vs Ivabradine in POTS

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ClinicalTrials.gov Identifier: NCT04186286
Recruitment Status : Recruiting
First Posted : December 4, 2019
Last Update Posted : March 9, 2021
Sponsor:
Collaborator:
Dysautonomia International
Information provided by (Responsible Party):
University of Calgary

Brief Summary:

1.0 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.

2.0 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.

3.0 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 20 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.


Condition or disease Intervention/treatment Phase
Postural Tachycardia Syndrome Drug: Ivabradine 4-week course Drug: Propranolol 4-week course Drug: Placebo 4-week course Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Crossover Study of Propranolol Versus Ivabradine in Postural Tachycardia Syndrome (POTS)
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 1st drug Ivabradine
Patients will take Ivabradine first followed by Propranolol and Placebo
Drug: Ivabradine 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of ivabradine.
Other Name: Lancora

Drug: Propranolol 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of propranolol.
Other Name: Inderal

Drug: Placebo 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of placebo

Active Comparator: 2nd drug Ivabradine
Patients will take either Propranolol or placebo first and then Ivabradine
Drug: Ivabradine 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of ivabradine.
Other Name: Lancora

Drug: Propranolol 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of propranolol.
Other Name: Inderal

Drug: Placebo 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of placebo

Active Comparator: 3rd drug Ivabradine
Patients will take Propranolol and placebo first and then Ivabradine
Drug: Ivabradine 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of ivabradine.
Other Name: Lancora

Drug: Propranolol 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of propranolol.
Other Name: Inderal

Drug: Placebo 4-week course
After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of placebo




Primary Outcome Measures :
  1. Change in HR [ Time Frame: 4 weeks ]
    the ∆HR from supine to standing on head-up tilt at 10 minutes after the 4 weeks each of patient taking Ivabradine, Propranolol and Placebo


Secondary Outcome Measures :
  1. Vanderbilt Orthostatic Symptoms Score [ Time Frame: 4 weeks ]
    change in symptom burden quantified by the VOSS at 10 minutes of head-up tilt after the 4 weeks each of patient taking Ivabradine, Propranolol and Placebo



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Postural Tachycardia Syndrome
  • Age between 18-60 years
  • Men and women are eligible
  • Able and willing to provide informed consent

Exclusion Criteria:

  • Seated resting heart rate < 70 bpm in the absence of rate-lowering medications
  • Supine blood pressure < 90/60 mmHg
  • Overt cause for postural tachycardia, i.e., acute dehydration, prolonged bed rest
  • Presence of underlying structural heart disease including:
  • Valvular disease (i.e. moderate or greater valvular stenosis or regurgitation)
  • History of heart failure
  • Greater than mild left ventricular systolic impairment
  • Hypertrophic cardiomyopathy
  • Known coronary artery disease or prior myocardial infarction
  • History of tachyarrhythmias including:
  • Supraventricular tachycardia, atrial tachycardia, atrial fibrillation / flutter
  • Ventricular tachyarrhythmias
  • Pre-existing long QT interval (e.g. known congenital long QT syndrome, or QT interval >500 ms)
  • History of sick sinus syndrome or high degree AV block
  • Presence of a pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device
  • Diabetes mellitus or history of hypoglycemic episodes
  • History of bronchospasm or uncontrolled asthma
  • Pregnant (by history or serum test) or breast-feeding
  • Inability to safely withdraw from existing beta-blockers or ivabradine prior to the study day
  • Concomitant use of class I and III antiarrhythmic agents, or non-dihydropyridine calcium channel blockers
  • Concomitant use of strong cytochrome P450 3A4 (CYP 3A4) inhibitors
  • Severe hepatic impairment
  • Any contraindication to propranolol or ivabradine not specifically listed above as per the product monographs.
  • Unable to give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04186286


Contacts
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Contact: Satish Raj, MD 403-210-6152 autonomic.research@ucalgary.ca
Contact: Shahana Safdar 403-220-8897 ssafdar@ucalgary.ca

Locations
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Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 1N4
Contact: Karolina Kogut    4032107627    kkogut@ucalgary.ca   
Contact: Shahana Safdar    14032208897    ssafdar@ucalgary.ca   
Sponsors and Collaborators
University of Calgary
Dysautonomia International
Investigators
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Principal Investigator: Satish R Raj, MD University of Calgary
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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT04186286    
Other Study ID Numbers: REB19-1437
First Posted: December 4, 2019    Key Record Dates
Last Update Posted: March 9, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Postural Orthostatic Tachycardia Syndrome
Tachycardia
Syndrome
Disease
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents