Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome (POTS)

Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome (a Double-blind Placebo-parallel Group Trial)

Postural orthostatic tachycardia syndrome (POTS) occurs in approximately 500,000 Americans, but predominates in women with a 5:1 ratio. Patients with POTS experience debilitating tachycardia upon postural changes such as standing that impairs their quality of life. Tachycardia is clinically defined as a heart rate greater than 100 beats/min; and in POTS patients, the prolonged heart rate increase is greater than 30 beats/min or increases to 120 beats/min within the first ten minutes of a diagnostic tilt table test without postural hypotension. There are currently no effective treatment methods for POTS. However, several studies suggest Ivabradine could be a main treatment option for POTS because Ivabradine specifically inhibits the f-channels (If) within the sinoatrial (SA) node, which slows the heart rate. Currently in the US, Ivabradine is mainly prescribed to treat chronic heart failure. It is well tolerated in patients, but it is not commonly prescribed for POTS. It has been also used for treatment of inappropriate sinus tachycardia with good benefit. The hypothesis for this experiment is that Ivabradine will reduce tachycardia and improve functional status in patients with POTS.

Study Overview

• Status: Completed
• Conditions: Postural Orthostatic Tachycardia Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Ivabradine

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects aged 18-65.
• Subjects must have POTS diagnosis (Hyperadrenergic Subtype with NE> 600pg/ml))
• Subjects with no structural heart disease
• Subject with no arrhythmias
• Subjects with norepinephrine levels greater than 600 pg/ml
• Subjects with normal CBC, Metabolic, and thyroid levels

Exclusion Criteria:

• Thyroid or adrenal disorders
• Drugs that interfere with Ivabradine (example: Cytochrome P450 drugs)
• Presentation of peripheral edema and discolored toes with peripheral autonomic neuropathy. Symptoms include: legs (reduced hair growth, cramps), toes (blue color), legs/feet (wounds, ulcers that do not heal), and muscles (numbness, heaviness)
• Subjects who have had a history of systemic illnesses (acute or chronic infectious); autoimmune/ inflammatory disease, cancer, COPD, anemia, diabetes, or psychiatric illness
• Subjects with resting heart rate< 60beats/min, atrial fibrillation, advanced AV blocks, sinus disease, and acute decompensated heart failure and severe hepatic impairment.
• Smokers or alcohol abuse
• Pregnant or breastfeeding mothers
• Woman of childbearing potential who are unwilling to use highly effective contraception during treatment and for an additional one month after discontinuing the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patient will consume one placebo pill twice a day for one month.	Drug: Placebo; A substance that has no therapeutic effect and will act as a control.
Experimental: Ivabradine; Patient will consume one dose of Ivabradine twice a day for one month.	Drug: Ivabradine; Ivabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Heart Rate	Orthostatic heart rate monitoring will be used to gauge heart rate changes.	Baseline and one month post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life Via SF-36 Survey	Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) The SF-36 has 36 questions and is an indicator of overall health status and is well-validated. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. The total score on the SF-36 ranges from 0 - 100 Lower scores = more disability, higher scores = less disability Sections: Vitality Physical functioning Bodily pain General health perceptions Physical role functioning Emotional role functioning Social role functioning Mental health	Baseline and one month post-treatment

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Amgen
• Investigators: Principal Investigator: Pam Taub, M.D., University of California, San Diego

Publications and helpful links

General Publications

• McDonald C, Frith J, Newton JL. Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. Europace. 2011 Mar;13(3):427-30. doi: 10.1093/europace/euq390. Epub 2010 Nov 9.
• Ewan V, Norton M, Newton JL. Symptom improvement in postural orthostatic tachycardia syndrome with the sinus node blocker ivabradine. Europace. 2007 Dec;9(12):1202. doi: 10.1093/europace/eum235. Epub 2007 Oct 19. No abstract available.
• Barzilai M, Jacob G. The Effect of Ivabradine on the Heart Rate and Sympathovagal Balance in Postural Tachycardia Syndrome Patients. Rambam Maimonides Med J. 2015 Jul 30;6(3):e0028. doi: 10.5041/RMMJ.10213.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2018
• Primary Completion (Actual): May 8, 2020
• Study Completion (Actual): May 8, 2020

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 7, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: POTS; ivabradine; tachycardia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Disease; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome
• Other Study ID Numbers: 170694

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No