Postural Orthostatic Tachycardia Syndrome
Conditions
Keywords
POTS, tachycardia, ivabradine
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.
Interventions
DRUGIvabradine
Ivabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node.
DRUGPlacebo
A substance that has no therapeutic effect and will act as a control.
Sponsors
Amgen
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Heart Rate | Baseline and one month post-treatment | Orthostatic heart rate monitoring will be used to gauge heart rate changes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life Via SF-36 Survey | 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 |
Countries
United States
Participant flow
Pre-assignment details
10 participants signed the consent form but did not pass the screening assessments. 1 participant signed the consent form and then withdrew prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo in Arm A, Ivabradine in Arm B In the first Arm, Patient will consume one placebo pill twice a day for one month.
Placebo: A substance that has no therapeutic effect and will act as a control.
In the second arm, patient will consume one dose of Ivabradine twice a day for one month.
Ivabradine: Ivabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node. | 16 |
| Ivabradine in Arm A, Placebo in Arm B In the first arm of the study, patient will consume one dose of Ivabradine twice a day for one month.
Ivabradine: Ivabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node.
In the second arm, patient will consume one placebo pill twice a day for one month.
Placebo: A substance that has no therapeutic effect and will act as a control. | 10 |
| Total | 26 |
Baseline characteristics
| Characteristic | Placebo in Arm A, Ivabradine in Arm B | Ivabradine in Arm A, Placebo in Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 10 Participants | 26 Participants |
| Age, Continuous | 35.75 years STANDARD_DEVIATION 10.7 | 27.8 years STANDARD_DEVIATION 11.15 | 34.8 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 10 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 10 Participants | 23 Participants |
| Region of Enrollment United States | 16 participants | 10 participants | 26 participants |
| Sex: Female, Male Female | 15 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 37 |
| other Total, other adverse events | 0 / 37 | 0 / 37 |
| serious Total, serious adverse events | 0 / 37 | 0 / 37 |
Outcome results
Primary
Change in Heart Rate
Orthostatic heart rate monitoring will be used to gauge heart rate changes.
Time frame: Baseline and one month post-treatment
Population: In total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Heart Rate | 17.0 beats per minute | Standard Deviation 10.4 |
| Ivabradine | Change in Heart Rate | 13.1 beats per minute | Standard Deviation 8.6 |
Secondary
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
Time frame: Baseline and one month post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Quality of Life Via SF-36 Survey | 44.1 units on a scale | Standard Deviation 22.4 |
| Ivabradine | Change in Quality of Life Via SF-36 Survey | 53.4 units on a scale | Standard Deviation 27 |