Postural Orthostatic Tachycardia SyndromePhase 3POTSNCT03182725
Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome
A Phase 3 study testing Ivabradine in people with Postural Orthostatic Tachycardia Syndrome, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome
- What is being tested?
- Ivabradine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Feb 2018to 8 May 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92093
About this study
Official title: 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.
- Being tested
- Ivabradine, Placebo
- Keywords
- POTS, tachycardia, ivabradine
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome, Tachycardia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
Ivabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node.
PlaceboDrug
A substance that has no therapeutic effect and will act as a control.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Patient will consume one placebo pill twice a day for one month. Receives: Drug: Placebo |
| Ivabradine | Experimental | Patient will consume one dose of Ivabradine twice a day for one month. Receives: Drug: Ivabradine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Heart Rate
Orthostatic heart rate monitoring will be used to gauge heart rate changes.
Measured: Baseline and one month post-treatment
Secondary outcomes (1)
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
Measured: Baseline and one month post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start6 Feb 2018
- Primary completion8 May 2020
- Study completion8 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Postural Orthostatic Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Pam Taub, MD, University of California, San Diego
- Investigators
- Pam Taub, M.D., Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03182725
- Sponsor's protocol ID
- 170694
- Acronym
- POTS
- Status last verified
- Jun 2021
- First submitted
- 7 Jun 2017
- Last updated
- 29 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 21062792Ewan 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.
PubMed 17951266Barzilai 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.
PubMed 26241226
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome (a Double-blind Placebo-parallel Group Trial)
- ClinicalTrials.gov ID
- NCT03182725
- Acronym / sponsor ID
- POTS / 170694
- Keywords
- POTS, tachycardia, ivabradine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 6 Feb 2018 (actual)
- Primary completion
- 8 May 2020 (actual)
- Study completion
- 8 May 2020 (actual)
- First posted
- 9 Jun 2017 (actual)
- Results
- Posted 29 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPatient will consume one placebo pill twice a day for one month. |
| Ivabradine | Experimental | Drug: IvabradinePatient will consume one dose of Ivabradine twice a day for one month. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IvabradineIvabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node. | Drug | Ivabradine |
| PlaceboA substance that has no therapeutic effect and will act as a control. | Drug | Placebo |
Primary outcome
Change in Heart Rate
Time frame: Baseline and one month post-treatment
Orthostatic heart rate monitoring will be used to gauge heart rate changes.
1 secondary outcome
Change in Quality of Life Via SF-36 Survey
Time frame: Baseline and one month post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21062792McDonald 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.
- Results publication: PubMed 17951266Ewan 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.
- Results publication: PubMed 26241226Barzilai 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.
Related trials for Postural Orthostatic Tachycardia Syndrome
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Recruiting
Ultrasound Guided Stellate Ganglion Block in Postural Tachycardia Syndrome
Postural Tachycardia Syndrome
Enrolling by invitationObservational study
Presentation of Young Adults With and Without Joint Hypermobility
Hypermobile Ehlers-Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome (POTS)
Active, not recruitingObservational study
POTS NET mRNA Functional Correlation With NET Activity
Postural Tachycardia Syndrome
Active, not recruiting
Acute Salt Handling in Orthostatic Intolerance
Postural Tachycardia Syndrome, Orthostatic Tachycardia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pam Taub, M.D. principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivabradine in people with Postural Orthostatic Tachycardia Syndrome, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Heart Rate (time frame: Baseline and one month post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03182725, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021.