Crossover Study of Propranolol vs Ivabradine in POTS

NCT04186286 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: REB19-1437
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Postural Tachycardia Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in HR

  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

  4 weeks

Secondary Outcomes (1)

• Vanderbilt Orthostatic Symptoms Score

  4 weeks

Study Arms (3)

1st drug Ivabradine

ACTIVE COMPARATOR

Patients will take Ivabradine first followed by Propranolol and Placebo

Drug: Ivabradine 4-week course; Drug: Propranolol 4-week course; Drug: Placebo 4-week course

2nd drug Ivabradine

ACTIVE COMPARATOR

Patients will take either Propranolol or placebo first and then Ivabradine

Drug: Ivabradine 4-week course; Drug: Propranolol 4-week course; Drug: Placebo 4-week course

3rd drug Ivabradine

ACTIVE COMPARATOR

Patients will take Propranolol and placebo first and then Ivabradine

Drug: Ivabradine 4-week course; Drug: Propranolol 4-week course; Drug: Placebo 4-week course

Interventions

Ivabradine 4-week course DRUG

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.

Also known as: Lancora

1st drug Ivabradine; 2nd drug Ivabradine; 3rd drug Ivabradine

Propranolol 4-week course DRUG

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.

Also known as: Inderal

1st drug Ivabradine; 2nd drug Ivabradine; 3rd drug Ivabradine

Placebo 4-week course DRUG

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

1st drug Ivabradine; 2nd drug Ivabradine; 3rd drug Ivabradine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Dysautonomia International: collaborator

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Interventions

Ivabradine; Propranolol

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Satish R Raj, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Satish Raj, MD

CONTACT

403-210-6152; autonomic.research@ucalgary.ca

Shahana Safdar

CONTACT

403-220-8897; ssafdar@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: December 4, 2019
• Study Start: February 1, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

CA (1)