Postural Tachycardia SyndromeEarly Phase 1NCT01210430
Local Vasoconstriction in Postural Tachycardia Syndrome
A Early Phase 1 study testing Losartan, Ascorbic Acid (Vitamin C) and Normal Saline in people with Postural Tachycardia Syndrome, run by New York Medical College at 1 site in United States.
Trial summary
The investigators study will determine how often blood flow regulation abnormalities and abnormalities of sympathetic regulation produced by nitric oxide, angiotensin-II, and oxidative stress occur in POTS and the mechanism(s) of POTS in individual patients. Specific causes for POTS may vary from patient to patient. Read more about this study
- Who is it for?
- Ages 14 to 29 yearsHealthy volunteers can take part
- Conditions the study is for
- Postural Tachycardia Syndrome
- What is being tested?
- Losartan, Ascorbic Acid (Vitamin C) and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Jun 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 14 to 29 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Cases will be between the ages of 14 and 29 years old referred for evaluation of orthostatic intolerance with 3 or more of the following symptoms for at least 3 months:
- dizziness
- nausea and vomiting
- palpitations
- fatigue
- headache
Show all 14Show fewer
- exercise intolerance
- blurred vision
- abnormal sweating heat.
- Cases will have the diagnosis of symptomatic postural tachycardia made during a screening tilt table test.
- Cases will have normal physical examination, and normal electrocardiographic and echocardiographic evaluations.
- Only those free from heart disease, and from systemic illness will be eligible to participate.
- This excludes patients with illnesses and disease states known to be associated with endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, morbid obesity and peripheral vascular disease.
- At the time of testing all patients and control subjects must refrain from vasoactive drugs for two weeks. Please check with us about any medication that you are taking.
Who cannot join
- Criteria for initial exclusion will include a condition known to be associated with endothelial dysfunction
- An active medical condition that may explain the diagnosis
- A previous medical condition with undocumented resolution that may explain the diagnosis
- Past or present major psychiatric disorder
- Substance abuse within 2 years before onset of symptoms.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York Medical College/Bradhurst building
Hawthorne, New York, 10532
About this study
The investigators study will determine how often blood flow regulation abnormalities and abnormalities of sympathetic regulation produced by nitric oxide, angiotensin-II, and oxidative stress occur in POTS and the mechanism(s) of POTS in individual patients. Specific causes for POTS may vary from patient to patient. Patients will be compared to healthy control subjects. There is a treatment arm with a medication (losartan) that reduces the binding of angiotensin and increases NO. If the investigators know the specific biochemical mechanism the investigators may be able to offer further specific treatments to specific patients.
Read the detailed description
Chronic orthostatic intolerance due to the postural tachycardia syndrome (POTS) severely impairs daily life in over a million Americans, mostly young women. POTS is defined by symptoms of orthostatic intolerance associated with excessive upright heart rate. While there is general agreement that abnormalities in vascular regulation and autonomic activity account for the tachycardia and symptoms of POTS, its pathophysiology is heterogeneous and only partially characterized.
The key feature of POTS is symptoms which are most prominent when standing. However, in some, findings are present supine (lying down) but worsened standing. Symptoms of POTS include dizziness in all patients, exercise provoked symptoms and thus exercise intolerance, excessive fatigue, nausea and abdominal pain, headache, shortness of breath and deep breathing, weakness, shakiness and postural anxiety, pallor, and neurocognitive loss (difficulty thinking). These occur on a day-to-day basis. The symptoms overlap with the case definition of chronic fatigue syndrome (CFS) and POTS is often found in CFS in the young. Fainting is relatively uncommon during daily life.
A major subset of POTS has increased peripheral resistance and low blood flow(LFP) related to increased angiotensin-II (Ang-II), and decreased nitric oxide (NO). NO deficits are reversed by Ang-II type-1 receptor (AT1R) blockade, ascorbic acid (AA) and tetrahydrobiopterin in skin suggesting the importance of oxidative stress. Preliminary data also suggest that the coupling of sympathetic nerve activity to blood vessel contraction is enhanced via ↑Ang-II and ↓NO. We hypothesize that this is due to activation of reactive oxygen species (ROS) including superoxide, which scavenges NO to generate peroxynitrite, and hydrogen peroxide. Combined measurements in the skin and the systemic circulation will be combined with local measurement of ROS production and sympathetic nerve activity will enable us to determine precisely how the autonomic nervous system is affected by the illness. Methods include cutaneous microdialysis to measure ROS, skin biopsy and blood tests to measure gene expression of nitric oxide synthase and Ang-II receptors, and peroneal microneurography to measure muscle sympathetic nerve activity (MSNA). Combined with ultrasonic femoral artery blood flow this will yield assessment of the interactions of nerves with the blood vessels that they control.
If we discover specific biochemical mechanisms of POTS in patients, then we may be able to specifically treat the defect.
- Conditions
- Postural Tachycardia Syndrome
- Being tested
- Losartan, Ascorbic Acid (Vitamin C), Normal Saline
- Keywords
- Postural Tachycardia Syndrome, Orthostatic Intolerance, Reactive Oxygen Species, Oxidative Stress, Angiotensin II, Nitric Oxide, Blood Flow, POTS, Ascorbic Acid, Vitamin C, Losartan
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome, Orthostatic Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Subjects will receive placebo or losartan for 4 weeks. Days 1-7, subjects will receive 12.5mg of Losartan or placebo. Days 7-14, subjects will receive 25mg of Losartan or placebo. Days 14-28, subjects will receive 50mg of Losartan or placebo.
Ascorbic Acid (Vitamin C)Drug
Also called Vitamin C
Subjects will receive 60mg/kg of Ascorbic Acid over 20 minutes followed by a maintenance infusion of 20mg/kg.
Normal SalineDrug
Subjects will receive 60mg/kg of normal saline over 20 minutes followed by a maintenance infusion of 20mg/kg of normal saline.
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Active comparator | Not described Receives: Drug: Losartan |
| Ascorbic Acid (VItamin C) | Active comparator | Not described Receives: Drug: Ascorbic Acid (Vitamin C) |
| Normal Saline | Placebo comparator | Not described Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Orthostatic tolerance measured by the heart rate and blood pressure response to upright tilt
Measured: 2 months
Secondary outcomes (1)
Sympathetic activation and blood flow measured by sympathetic nerve recordings and Doppler blood flow in the leg
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2010 (estimated)
- Study startJul 2010
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Tachycardia SyndromeStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Julian Stewart, New York Medical College
- Investigators
- Julian M Stewart, MD, PhD, Principal investigator, New York Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01210430
- Sponsor's protocol ID
- 2R01HL074873-06A2
- Status last verified
- Jun 2021
- First submitted
- 19 Aug 2010
- Last updated
- 10 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Local Vasoconstriction in Postural Tachycardia Syndrome
- ClinicalTrials.gov ID
- NCT01210430
- Acronym / sponsor ID
- 2R01HL074873-06A2
- Conditions
- Postural Tachycardia Syndrome
- Keywords
- Postural Tachycardia Syndrome, Orthostatic Intolerance, Reactive Oxygen Species, Oxidative Stress, Angiotensin II, Nitric Oxide, Blood Flow, POTS
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- New York Medical CollegeUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 28 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators study will determine how often blood flow regulation abnormalities and abnormalities of sympathetic regulation produced by nitric oxide, angiotensin-II, and oxidative stress occur in POTS and the mechanism(s) of POTS in individual patients. Specific causes for POTS may vary from patient to patient. Patients will be compared to healthy control subjects. There is a treatment arm with a medication (losartan) that reduces the binding of angiotensin and increases NO. If the investigators know the specific biochemical mechanism the investigators may be able to offer further specific treatments to specific patients.
Detailed description
Chronic orthostatic intolerance due to the postural tachycardia syndrome (POTS) severely impairs daily life in over a million Americans, mostly young women. POTS is defined by symptoms of orthostatic intolerance associated with excessive upright heart rate. While there is general agreement that abnormalities in vascular regulation and autonomic activity account for the tachycardia and symptoms of POTS, its pathophysiology is heterogeneous and only partially characterized.
The key feature of POTS is symptoms which are most prominent when standing. However, in some, findings are present supine (lying down) but worsened standing. Symptoms of POTS include dizziness in all patients, exercise provoked symptoms and thus exercise intolerance, excessive fatigue, nausea and abdominal pain, headache, shortness of breath and deep breathing, weakness, shakiness and postural anxiety, pallor, and neurocognitive loss (difficulty thinking). These occur on a day-to-day basis. The symptoms overlap with the case definition of chronic fatigue syndrome (CFS) and POTS is often found in CFS in the young. Fainting is relatively uncommon during daily life.
A major subset of POTS has increased peripheral resistance and low blood flow(LFP) related to increased angiotensin-II (Ang-II), and decreased nitric oxide (NO). NO deficits are reversed by Ang-II type-1 receptor (AT1R) blockade, ascorbic acid (AA) and tetrahydrobiopterin in skin suggesting the importance of oxidative stress. Preliminary data also suggest that the coupling of sympathetic nerve activity to blood vessel contraction is enhanced via ↑Ang-II and ↓NO. We hypothesize that this is due to activation of reactive oxygen species (ROS) including superoxide, which scavenges NO to generate peroxynitrite, and hydrogen peroxide. Combined measurements in the skin and the systemic circulation will be combined with local measurement of ROS production and sympathetic nerve activity will enable us to determine precisely how the autonomic nervous system is affected by the illness. Methods include cutaneous microdialysis to measure ROS, skin biopsy and blood tests to measure gene expression of nitric oxide synthase and Ang-II receptors, and peroneal microneurography to measure muscle sympathetic nerve activity (MSNA). Combined with ultrasonic femoral artery blood flow this will yield assessment of the interactions of nerves with the blood vessels that they control.
If we discover specific biochemical mechanisms of POTS in patients, then we may be able to specifically treat the defect.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Losartan | Active comparator | Drug: Losartan |
| Ascorbic Acid (VItamin C) | Active comparator | Drug: Ascorbic Acid (Vitamin C) |
| Normal Saline | Placebo comparator | Drug: Normal Saline |
Who may qualify
- Ages
- 14 to 29 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Cases will be between the ages of 14 and 29 years old referred for evaluation of orthostatic intolerance with 3 or more of the following symptoms for at least 3 months:
- Cases will have the diagnosis of symptomatic postural tachycardia made during a screening tilt table test.
- Cases will have normal physical examination, and normal electrocardiographic and echocardiographic evaluations.
- Only those free from heart disease, and from systemic illness will be eligible to participate.
- This excludes patients with illnesses and disease states known to be associated with endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, morbid obesity and peripheral vascular disease.
Key exclusion criteria (5 listed)
- Criteria for initial exclusion will include a condition known to be associated with endothelial dysfunction
- An active medical condition that may explain the diagnosis
- A previous medical condition with undocumented resolution that may explain the diagnosis
- Past or present major psychiatric disorder
- Substance abuse within 2 years before onset of symptoms.
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 |
|---|---|---|
| LosartanSubjects will receive placebo or losartan for 4 weeks. Days 1-7, subjects will receive 12.5mg of Losartan or placebo. Days 7-14, subjects will receive 25mg of Losartan or placebo. Days 14-28, subjects will receive 50mg of Losartan or placebo. | Drug | Losartan |
| Ascorbic Acid (Vitamin C)Also: Vitamin CSubjects will receive 60mg/kg of Ascorbic Acid over 20 minutes followed by a maintenance infusion of 20mg/kg. | Drug | Ascorbic Acid (VItamin C) |
| Normal SalineSubjects will receive 60mg/kg of normal saline over 20 minutes followed by a maintenance infusion of 20mg/kg of normal saline. | Drug | Normal Saline |
Primary outcome
Orthostatic tolerance measured by the heart rate and blood pressure response to upright tilt
Time frame: 2 months
1 secondary outcome
Sympathetic activation and blood flow measured by sympathetic nerve recordings and Doppler blood flow in the leg
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
Related trials for Postural Tachycardia Syndrome
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 recruitingPhase 1/2
Treatment of Orthostatic Intolerance
Tachycardia, Chronic Orthostatic Intolerance
Active, not recruiting
Intravenous (IV) Saline and Exercise in Postural Tachycardia Syndrome (POTS)
Postural Tachycardia Syndrome
Active, not recruitingObservational study
POTS NET mRNA Functional Correlation With NET Activity
Postural Tachycardia Syndrome
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.
Julian M Stewart, MD, PhD principal investigator
New York Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Losartan, Ascorbic Acid (Vitamin C) and Normal Saline in people with Postural Tachycardia Syndrome, run by New York Medical College 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 14 inclusion and 5 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 10 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Orthostatic tolerance measured by the heart rate and blood pressure response to upright tilt (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2021.