search
Back to results

Northera Improves Postural Tachycardia Syndrome (POTS) and Postural Vasovagal Syncope (VVS)

Primary Purpose

Postural Tachycardia Syndrome (POTS), Vasovagal Syncope (VVS), Fainting

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Northera (Droxidopa)
Placebo
Northera (Droxidopa)
Placebo
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postural Tachycardia Syndrome (POTS) focused on measuring Postural Tachycardia Syndrome (POTS), Vasovagal Syncope (VVS), Fainting, Orthostatic Intolerance, Droxidopa, Northera

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Both male and female participants are being studied
  • Ages 18-30 years old
  • POTS cases will be referred for day-to-day Orthostatic Intolerance (OI) with ≥3 symptoms for >6 months.
  • POTS will be confirmed by medical history indicating chronic OI, and by a prior 700 tilt table test or standing test showing excessive tachycardia and symptoms OI in the absence of hypotension.
  • VVS (fainting) subjects will have at least 2 episodes of postural VVS during the past calendar year.
  • Healthy volunteers will be included for Study #1

Exclusion Criteria:

  • Only those free from all systemic illnesses will be eligible to participate. This excludes patients with illnesses associated with autonomic dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, obesity, cancer, supine or upright hypertension, and peripheral vascular disease.
  • No subjects will be taking neurally active, or vasoactive drugs. Prior medication will be stopped for at least 2 weeks.

Sites / Locations

  • New York Medical College/Bradhurst building

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Placebo Comparator

Arm Label

Northera-single dose

Northera- chronic administration

Arm Description

Study #1 -Does single large dose (600mg) of Northera improve upright hemodynamics and orthostatic intolerance in POTS and VVS

Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day.

Outcomes

Primary Outcome Measures

Study #1 and Study #2 - Splanchnic and lower extremity pooling (physiological parameter)
Splanchnic and lower extremity pooling will be measured before, during, and after upright tilt. The investigators will use both venous occlusion plethysmography and impedance plethysmography. Venous occlusion plethysmography are made in ml/min by rapidly inflating cuffs to a pressure of 45mmHg and then computing the slope of the time dependent increase in cross limb section. During impedance plethysmography, a Tetrapolar High Resolution Impedance monitor 4-channel digital IPG is used to detect changes in regional blood volume and blood flow in ml/min
Study #2 -Quality of Life measured by self reporting questionnaire (RAND-36)
The investigators will test whether chronic administration of Northera (Droxidopa) in escalating dose improves quality of life. Quality of life will be measured by the RAND-36 questionnaire. The RAND-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. (2-4)
Study #2 -Quality of Life measured by self reporting questionnaire (COMPASS 31)
The investigators will test whether chronic administration of Northera (Droxidopa) in escalating dose improves quality of life. Quality of life will be measured by the RAND-36 questionnaire (as shown in the above primary outcome) as well as the COMPASS 31 questionnaire. The COMPASS 31 "was developed as a self-assessment instrument of autonomic symptoms and function that is up-to-date, broadly applicable, easy to administer in a short amount of time, and based on a scientific approach. It was designed to provide a global autonomic severity score and domain scores that are both clinically and scientifically meaningful." "COMPASS 31 is based on the well-established ASP [Autonomic Symptom Profile], a comprehensive questionnaire assessing autonomic symptoms across multiple domains." (1)

Secondary Outcome Measures

Study #1 and Study #2 -Blood pressure (BP)
During laboratory testing, blood pressure will be continuously monitored in mmHg
Study #1 and Study #2 -Heart rate (HR)
During laboratory testing, heart rate will be continuously monitored in beats/minute.

Full Information

First Posted
September 21, 2015
Last Updated
April 5, 2022
Sponsor
New York Medical College
Collaborators
Lundbeck LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT02558972
Brief Title
Northera Improves Postural Tachycardia Syndrome (POTS) and Postural Vasovagal Syncope (VVS)
Official Title
Northera Improves Postural Tachycardia Syndrome (POTS) and Postural
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 2015 (undefined)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College
Collaborators
Lundbeck LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Vasovagal syncope (VVS, simple faint) is the most common cause of transient loss of consciousness and represents the acute episodic form of orthostatic intolerance (OI). Postural tachycardia syndrome (POTS) is the common chronic form of OI. Both are defined by debilitating symptoms and signs while upright relieved by recumbency. Northera should therefore improve both sympathetic splanchnic arterial vasoconstriction and sympathetic splanchnic venoconstriction in POTS and VVS, and may represent an ideal drug to improve the orthostatic response in POTS and VVS.
Detailed Description
Vasovagal syncope (VVS, simple faint) is the most common cause of transient loss of consciousness and represents the acute episodic form of orthostatic intolerance (OI). Postural tachycardia syndrome (POTS) is the common chronic form of OI. Both are defined by debilitating symptoms and signs while upright relieved by recumbency. Pathophysiological mechanisms have remained elusive. Most POTS patients and all VVS patients have normal supine resting hemodynamics but excessively redistribute blood flow and blood volume from the central pool to the splanchnic vasculature because of defective splanchnic arterial vasoconstriction and venoconstriction. While peripheral and splanchnic arterial vasoconstriction depend primarily on post-junctional alpha-1 adrenergic receptors, splanchnic venoconstriction also depends on post-junctional alpha-2 adrenergic receptors. Consequently, selective alpha-1 agonists such as midodrine may not produce sufficient splanchnic venoconstriction to compensate for splanchnic pooling in POTS and VVS. Such alpha adrenergic subtype restrictions do not apply to Northera (droxidopa) because it is a norepinephrine (NE) prodrug and therefore increases the amount of synaptic NE that can then bind to both alpha-2 and alpha-1 receptors. Northera should therefore improve both sympathetic splanchnic arterial vasoconstriction and sympathetic splanchnic venoconstriction in POTS and VVS, and may represent an ideal drug to improve the orthostatic response in POTS and VVS. We will test the hypothesis that Northera, in appropriate dose, improves the splanchnic adrenergic deficits that initiate POTS and postural VVS and in sufficient daily dose improves quality of life in these patients. To accomplish this, the investigator will recruit 10 POTS patients aged 18-30 years, 10 similarly aged patients with 2 or more episodes of VVS in the past year (thus defining recurrent VVS) and 10 age and gender matched healthy volunteer control subjects with the following specific aims:

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postural Tachycardia Syndrome (POTS), Vasovagal Syncope (VVS), Fainting
Keywords
Postural Tachycardia Syndrome (POTS), Vasovagal Syncope (VVS), Fainting, Orthostatic Intolerance, Droxidopa, Northera

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Northera-single dose
Arm Type
Placebo Comparator
Arm Description
Study #1 -Does single large dose (600mg) of Northera improve upright hemodynamics and orthostatic intolerance in POTS and VVS
Arm Title
Northera- chronic administration
Arm Type
Placebo Comparator
Arm Description
Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day.
Intervention Type
Drug
Intervention Name(s)
Northera (Droxidopa)
Intervention Description
Study #1 -Supine monitoring is performed for 30 minutes before administration of a single 600mg oral dose of Northera or placebo assigned randomly, After 2 hours supine a 70 degree upright tilt will performed for 10 minutes. On another day, subjects previously given Northera will receive placebo and vice versa and studies repeated.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Study #1 -Supine monitoring is performed for 30 minutes before administration of a single 600mg oral dose of Northera or placebo assigned randomly, After 2 hours supine a 70 degree upright tilt will performed for 10 minutes. On another day, subjects previously given Northera will receive placebo and vice versa and studies repeated.
Intervention Type
Drug
Intervention Name(s)
Northera (Droxidopa)
Intervention Description
Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day. Doses will be reduced to the preceding dose if systolic BP>140mmHg or diastolic BP>80mmHg measured in the seated position at home using an automated ambulatory blood pressure cuff 2 hours after receiving an oral dose. Doses will also be reduced if supine BP measured with the head of the bed elevated upon awakening in the morning exceeds 150/90 mmHg. Following a 1 week wash out period, subjects will receive the alternative treatment for 2 additional weeks and instrumented laboratory studies repeated.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day. Doses will be reduced to the preceding dose if systolic BP>140mmHg or diastolic BP>80mmHg measured in the seated position at home using an automated ambulatory blood pressure cuff 2 hours after receiving an oral dose. Doses will also be reduced if supine BP measured with the head of the bed elevated upon awakening in the morning exceeds 150/90 mmHg. Following a 1 week wash out period, subjects will receive the alternative treatment for 2 additional weeks and instrumented laboratory studies repeated.
Primary Outcome Measure Information:
Title
Study #1 and Study #2 - Splanchnic and lower extremity pooling (physiological parameter)
Description
Splanchnic and lower extremity pooling will be measured before, during, and after upright tilt. The investigators will use both venous occlusion plethysmography and impedance plethysmography. Venous occlusion plethysmography are made in ml/min by rapidly inflating cuffs to a pressure of 45mmHg and then computing the slope of the time dependent increase in cross limb section. During impedance plethysmography, a Tetrapolar High Resolution Impedance monitor 4-channel digital IPG is used to detect changes in regional blood volume and blood flow in ml/min
Time Frame
2 weeks
Title
Study #2 -Quality of Life measured by self reporting questionnaire (RAND-36)
Description
The investigators will test whether chronic administration of Northera (Droxidopa) in escalating dose improves quality of life. Quality of life will be measured by the RAND-36 questionnaire. The RAND-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. (2-4)
Time Frame
6 weeks
Title
Study #2 -Quality of Life measured by self reporting questionnaire (COMPASS 31)
Description
The investigators will test whether chronic administration of Northera (Droxidopa) in escalating dose improves quality of life. Quality of life will be measured by the RAND-36 questionnaire (as shown in the above primary outcome) as well as the COMPASS 31 questionnaire. The COMPASS 31 "was developed as a self-assessment instrument of autonomic symptoms and function that is up-to-date, broadly applicable, easy to administer in a short amount of time, and based on a scientific approach. It was designed to provide a global autonomic severity score and domain scores that are both clinically and scientifically meaningful." "COMPASS 31 is based on the well-established ASP [Autonomic Symptom Profile], a comprehensive questionnaire assessing autonomic symptoms across multiple domains." (1)
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Study #1 and Study #2 -Blood pressure (BP)
Description
During laboratory testing, blood pressure will be continuously monitored in mmHg
Time Frame
2 weeks
Title
Study #1 and Study #2 -Heart rate (HR)
Description
During laboratory testing, heart rate will be continuously monitored in beats/minute.
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Both male and female participants are being studied Ages 18-30 years old POTS cases will be referred for day-to-day Orthostatic Intolerance (OI) with ≥3 symptoms for >6 months. POTS will be confirmed by medical history indicating chronic OI, and by a prior 700 tilt table test or standing test showing excessive tachycardia and symptoms OI in the absence of hypotension. VVS (fainting) subjects will have at least 2 episodes of postural VVS during the past calendar year. Healthy volunteers will be included for Study #1 Exclusion Criteria: Only those free from all systemic illnesses will be eligible to participate. This excludes patients with illnesses associated with autonomic dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, obesity, cancer, supine or upright hypertension, and peripheral vascular disease. No subjects will be taking neurally active, or vasoactive drugs. Prior medication will be stopped for at least 2 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julian M Stewart, M.D., Ph.D.
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York Medical College/Bradhurst building
City
Hawthorne
State/Province
New York
ZIP/Postal Code
10532
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23218087
Citation
Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W. COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score. Mayo Clin Proc. 2012 Dec;87(12):1196-201. doi: 10.1016/j.mayocp.2012.10.013.
Results Reference
background
Citation
http: and www.rand.org/health/surveys_tools/mos/mos_core_36item.html. 36-Item Short Form Survey from the RAND Medical Outcomes Study. 2014.
Results Reference
background
PubMed Identifier
1301123
Citation
Hays RD, Shapiro MF. An overview of generic health-related quality of life measures for HIV research. Qual Life Res. 1992 Apr;1(2):91-7. doi: 10.1007/BF00439716.
Results Reference
background
PubMed Identifier
1593914
Citation
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
Results Reference
background
Links:
URL
http://syncope.org
Description
The Center for Hypotension

Learn more about this trial

Northera Improves Postural Tachycardia Syndrome (POTS) and Postural Vasovagal Syncope (VVS)

We'll reach out to this number within 24 hrs