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Autonomic Determinants of POTS - Pilot1

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ClinicalTrials.gov Identifier: NCT04050410
Recruitment Status : Recruiting
First Posted : August 8, 2019
Last Update Posted : January 13, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Andre' Diedrich, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE August 2, 2019
First Posted Date  ICMJE August 8, 2019
Last Update Posted Date January 13, 2021
Actual Study Start Date  ICMJE August 27, 2019
Estimated Primary Completion Date July 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
Change in Orthostatic Symptom Burden [delta (delta VOSS)] [ Time Frame: after 30 min supine to after 15 min upright (delta VOSS), 2-3 hours after placebo or moxonidine intake [delta (delta VOSS)]. ]
VOSS is a validated questionnaire that consists of 9 items: mental clouding, blurred vision, shortness of breath, rapid heartbeat, tremulousness, chest discomfort, headache, lightheadedness, and nausea. Each item is scored on a 0 to 10 scale (with 0 reflecting absence of symptoms), and the change of the total scores (range: 0-90) from supine to upright postures (delta VOSS) will be used as a measure of orthostatic symptom burden. The primary outcome measure will be the difference in orthostatic symptom burden [delta (delta VOSS)] following placebo vs. moxonidine administration.
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
Change in Vanderbilt Orthostatic Symptom Score (delta VOSS) [ Time Frame: after 30 min supine to after 15 min upright, 2-3 hours after drug intake ]
VOSS is a validated questionnaire that consists of 9 items: mental clouding, blurred vision, shortness of breath, rapid heartbeat, tremulousness, chest discomfort, headache, lightheadedness, and nausea. Each item is scored on a 0 to 10 scale (with 0 reflecting absence of symptoms), and the change of the total scores (range: 0-90) from supine to upright postures will be used as a measure of orthostatic symptom burden.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
Change in Orthostatic Change in Heart Rate [delta (delta HR)] [ Time Frame: after 30 min supine to after 15 min upright (delta HR), 2-3 hours after placebo or moxonidine intake [delta (delta HR)]. ]
Difference in heart rate change from supine to upright postures (delta HR) following placebo vs. moxonidine administration.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
Orthostatic Change in Heart Rate (delta HR) [ Time Frame: after 30 min supine to after 15 min upright, 2-3 hours after drug intake ]
Heart rate change from supine to upright postures
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autonomic Determinants of POTS - Pilot1
Official Title  ICMJE Autonomic Determinants of Postural Tachycardia Syndrome (Acute Pilot Study 1)
Brief Summary Postural tachycardia syndrome (POTS) is a relatively common condition affecting mostly otherwise healthy young women. It is the cause of significant disability and an impairment in quality of life. These patients have high heart rate and symptoms during standing. Many of these patients are disabled and have a poor quality of life. The sympathetic nerves are part of the nervous system that helps to maintain normal blood pressures and heart rates during activities of daily life. The purpose of this study is to determine the importance of sympathetic activation as a cause of orthostatic symptoms. The investigators will assess the effects of a blood pressure medication (Moxonidine) on the symptoms during standing. Moxonidine lowers sympathetic activity. The investigators believe patients with high resting sympathetic activity might benefit from Moxonidine. It might reduce high heart rate and improve symptoms during standing. This study should help clinicians and the growing population of patients with POTS gain a better understanding of this disorder and find more personalized treatment.
Detailed Description

Postural tachycardia syndrome (POTS) is a relatively common condition affecting mostly otherwise healthy young women. It is the cause of significant disability and an impairment in quality of life of a magnitude comparable to patients with chronic obstructive pulmonary disease or congestive heart failure. It is characterized by sympathetic activation with an exaggerated orthostatic tachycardia that responds to low doses of beta-blockers. The underlying pathophysiology of this disorder and the nature of this sympathetic activation is not clear and is likely heterogeneous. In many patients this sympathetic activation could be an appropriate compensatory response to hypovolemia, deconditioning or partial neuropathy.

The investigators have identified a subset of patients in whom sympathetic activation appears to be a primary phenomenon. These patients are characterized by high central sympathetic outflow, as determined by muscle sympathetic nerve activity (MSNA) above the upper 95% confidence interval for the group. This "hyperadrenergic" phenotype is associated with a paradoxical increase in blood pressure on standing and exaggerated pressor response to the vasoconstrictive phase of the Valsalva maneuver, and clinical observations suggest they improve clinically when treated with central sympatholytics.

The investigators propose to test the hypothesis that there is a subset of POTS patients with a central sympathetic activation as the primary pathophysiology. In an acute double blind, placebo-controlled, randomized study, the investigators propose that administration of the central sympatholytic moxonidine will improve orthostatic symptoms and abnormalities in orthostatic hemodynamics, as well as sympathetic outflow.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Randomized, double-blind, placebo-controlled crossover
Masking: Double (Participant, Investigator)
Masking Description:
Subject and investigator will be blinded. The randomization will be generated by the pharmacy. A staff member of the Autonomic Dysfunction Center who is not involved in the study will keep secretly the randomization blinding table for emergencies. Blinding will be broken for intermediate data analysis and in case of emergencies if necessary. The blinding will be broken at the end of statistical analysis for interpretation of results.
Primary Purpose: Other
Condition  ICMJE Postural Tachycardia Syndrome
Intervention  ICMJE
  • Drug: Moxonidine
    active drug given as 1 dose
    Other Name: Physiotens
  • Drug: Placebo
    placebo pill given as 1 dose
    Other Name: inactive pill
Study Arms  ICMJE
  • Experimental: Moxonidine
    Patients will receive a single oral dose of moxonidine 0.4 mg.
    Intervention: Drug: Moxonidine
  • Placebo Comparator: Placebo
    Patients will receive a single oral dose of placebo.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 20, 2019)
48
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2019)
70
Estimated Study Completion Date  ICMJE December 31, 2025
Estimated Primary Completion Date July 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • female/male subjects, age 18-55 years,
  • criteria for postural tachycardia syndrome (POTS):

    1. a heart rate increase of ≥30 beats/min within 10 minutes of upright posture;
    2. lack of orthostatic hypotension (blood pressure fall ≥ 20/10 mmHg within 10 minutes of standing); and
    3. chronic symptoms during upright posture over at least 6 months, in the absence of any other acute cause.
  • in the follicular phase of the menstrual cycle (day 5-13 of a 28-day cycle)
  • POTS with primary central sympathetic activation (psPOTS) as defined as having resting muscle sympathetic nerve activity (MSNA) greater than or equal to 25 bursts/min
  • able and willing to provide informed consent.

Exclusion Criteria:

  • pregnancy,
  • smoker,
  • BMI>30 kg/m2,
  • deconditioned status (if available VO2max<80% of predicted)
  • unable to withdraw from medications known to affect autonomic function, blood pressure or blood volume
  • systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies.
  • Arteriosclerotic disease of carotid artery. History of neck surgery.
  • conditions associated with inflammatory processes, such as coronary artery disease, hypertension, smoking, hypercholesterolemia (or on statin therapy), rheumatoid arthritis, diabetes
  • treatment with oral corticosteroids, current infections (e.g., urinary tract infection), or use of non-steroidal anti-inflammatory drugs
  • other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Emily C Smith, RN 615 875-1516 autonomics@vumc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04050410
Other Study ID Numbers  ICMJE VANDERBILT_IRB_190703
R56HL142583 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Andre' Diedrich, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: André Diedrich, MD Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP