Clinical trial NCT03182725: Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome
Official title: Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome (a Double-blind Placebo-parallel Group Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postural Orthostatic Tachycardia Syndrome
Keywords: POTS
tachycardia
ivabradine
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2017-06-09
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change in Heart Rate
timeFrame: Baseline and one month post-treatment
Secondary outcomes:
measure: Change in Quality of Life Via SF-36 Survey
timeFrame: Baseline and one month post-treatment
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
Study officials:
affiliation: University of California, San Diego
name: Pam Taub, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.