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

• ClinicalTrials.gov Identifier: NCT03182725
• Recruitment Status: Completed
• First Posted: June 9, 2017
• Results First Posted: June 29, 2021
• Last Update Posted: June 29, 2021
• Sponsor: University of California, San Diego
• Collaborator: Amgen
• Information provided by (Responsible Party): Pam Taub, MD, University of California, San Diego

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Postural Orthostatic Tachycardia Syndrome	Drug: Ivabradine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: 20 patients with POTS will receive Ivabradine treatment vs placebo for one month. Then there will be a one-month wash out period prior to the cross over in which patients who received Ivabradine will receive the placebo, and patients who initially were on placebo will now receive Ivabradine.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome (a Double-blind Placebo-parallel Group Trial)
• Actual Study Start Date: February 6, 2018
• Actual Primary Completion Date: May 8, 2020
• Actual Study Completion Date: May 8, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in Heart Rate [ Time Frame: Baseline and one month post-treatment ]
   Orthostatic heart rate monitoring will be used to gauge heart rate changes.

Secondary Outcome Measures :

1. Change in Quality of Life Via SF-36 Survey [ Time Frame: Baseline and one month post-treatment ]

   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of California, San Diego

La Jolla, California, United States, 92093

Sponsors and Collaborators

University of California, San Diego

Amgen

Investigators

• Principal Investigator: Pam Taub, M.D.; University of California, San Diego

  Study Documents (Full-Text)

Documents provided by Pam Taub, MD, University of California, San Diego:

Study Protocol and Statistical Analysis Plan  [PDF] March 7, 2020

Informed Consent Form  [PDF] March 7, 2020

More Information

Publications of Results:

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. Epub 2007 Oct 19.

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). doi: 10.5041/RMMJ.10213.

• Responsible Party: Pam Taub, MD, Associate Professor of Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03182725
• Other Study ID Numbers: 170694
• First Posted: June 9, 2017
• Results First Posted: June 29, 2021
• Last Update Posted: June 29, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pam Taub, MD, University of California, San Diego:

POTS; tachycardia; ivabradine

Additional relevant MeSH terms:

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