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

NCT02558972 | Terminated Phase 2 DMC

• 1 other identifier: L-11,388
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Postural Tachycardia Syndrome (POTS); Vasovagal Syncope (VVS); Fainting; Orthostatic Intolerance; Droxidopa; Northera

Outcome Measures

Primary Outcomes (3)

• 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

  2 weeks

• 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)

  6 weeks

• 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)

  6 weeks

Secondary Outcomes (2)

• Study #1 and Study #2 -Blood pressure (BP)

  2 weeks

• Study #1 and Study #2 -Heart rate (HR)

  2 weeks

Study Arms (2)

Northera-single dose

PLACEBO COMPARATOR

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

Drug: Northera (Droxidopa); Drug: Placebo

Northera- chronic administration

PLACEBO COMPARATOR

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.

Drug: Northera (Droxidopa); Drug: Placebo

Interventions

Northera (Droxidopa) DRUG

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.

Northera-single dose

Placebo DRUG

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.

Northera-single dose

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York Medical College: lead
• Lundbeck LLC: collaborator

Study Sites (1)

New York Medical College/Bradhurst building

Hawthorne, New York, 10532, United States

Location

Related Publications (4)

• 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.

  PMID: 23218087 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 1301123 BACKGROUND

• 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.

  PMID: 1593914 BACKGROUND

Related Links

• The Center for Hypotension

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Syncope, Vasovagal; Syncope; Orthostatic Intolerance

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Julian M Stewart, M.D., Ph.D.

  New York Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Physiology

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 24, 2015
• Study Start: September 1, 2015
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

US (1)