Back to resultsAutonomic Determinants of POTS - Pilot 2
Primary Purpose
Postural Tachycardia Syndrome
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo oral tablet
Moxonidine Pill
Sponsored by
About this trial
This is an interventional other trial for Postural Tachycardia Syndrome focused on measuring postural tachycardia syndrome, hyperadrenergic, moxonidine, sympatholytic, orthostatic symptoms, POTS
Eligibility Criteria
Inclusion Criteria:
meets criteria for postural tachycardia syndrome (POTS)
- a heart rate increase of ≥30 beats/min within 10 minutes of upright posture;
- lack of orthostatic hypotension (blood pressure fall ≥ 20/10 mmHg within 3 minutes of standing); and
- 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 (days 5-13 of a 28-day cycle)
- POTS with primary central sympathetic activation (psPOTS) as defined as having resting MSNA ≥ 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.
Sites / Locations
- Vanderbilt University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Moxonidine then Placebo
Placebo then Moxonidine
Arm Description
After screening/baseline evaluations, patients will be discharged home on moxonidine 0.2-0.4 mg/day PO. After two weeks, the patients will be re-admitted for study testing while on moxonidine. At completion of this testing, patients will start taking matching placebo once daily PO to be continued at home. After two, the patients will be re-admitted for study testing while on placebo.
After screening/baseline evaluations, patients will be discharged home on placebo identical to moxonidine once daily PO. After two weeks, the patients will be re-admitted for study testing while on placebo. At completion of this testing, patients will start taking moxonidine 0.2-0.4 mg/day PO to be continued at home. After two weeks, the patients will be re-admitted for study testing while on moxonidine.
Outcomes
Primary Outcome Measures
Change in Orthostatic Symptom Burden [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 4 weeks of placebo vs. moxonidine treatment.
Secondary Outcome Measures
Change in Orthostatic Change in Heart Rate [delta (delta HR)]
Difference in heart rate change from supine to upright postures (delta HR) following 4 weeks of placebo vs. moxonidine treatment [delta (delta HR)].
Full Information
NCT ID
NCT04140721
First Posted
October 24, 2019
Last Updated
January 19, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT04140721
Brief Title
Autonomic Determinants of POTS - Pilot 2
Official Title
Autonomic Determinants of Postural Tachycardia Syndrome (Chronic Pilot Study 2)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2021 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Postural tachycardia syndrome (POTS) is a relatively common condition affecting mostly otherwise healthy young women. These patients have high heart rate and disabling symptoms during standing. Quality of life may be poor. The sympathetic nerves in the autonomic nervous system help 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
Patients with POTS experience symptoms and an increase in heart rate≥30 beats/min with standing in the absence of orthostatic hypotension. As a result of considerable functional impairment, individuals with POTS are often unable to attend school or work. There is agreement that POTS is a heterogeneous disorder with multiple overlapping pathophysiologies proposed to underlie the clinical phenotype of patients. It would be important to define the underlying pathophysiological mechanisms in an individual patient to design optimal therapy. Our overarching hypothesis is that there is a subset of POTS patients (psPOTS) with a central sympathetic activation as the primary pathophysiology. We have characterized these patients by an increase in muscle sympathetic nerve activity (MSNA, a reflection of central sympathetic outflow) even at rest. In this project, we will focus on the role of primary sympathetic activation in the pathogenesis of POTS. Direct neural recordings of sympathetic activity, central sympathetic inhibition and extensive autonomic phenotyping will enable us to identify and correct the primary pathophysiology to optimally benefit psPOTS patients. This is a mechanistic study, designed to assess the effects of 4 weeks of central sympatholysis with moxonidine on orthostatic tachycardia and symptoms (Specific Aim 1), hypovolemia (Specific Aim 2) and central and peripheral baroreflex properties (Specific Aim 3) in a randomized, crossover design with POTS patients having elevated resting sympathetic nerve activity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postural Tachycardia Syndrome
Keywords
postural tachycardia syndrome, hyperadrenergic, moxonidine, sympatholytic, orthostatic symptoms, POTS
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Model Description
randomized, double blind, crossover design
Masking
ParticipantInvestigator
Masking Description
Vanderbilt's Investigational Pharmacy will randomly assign participants to the moxonidine/placebo or placebo/moxonidine arm of the study. They will also provide the active drug and matching placebo. The medication distribution list will be kept by a dedicated person not involved in the study.
Allocation
Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Moxonidine then Placebo
Arm Type
Experimental
Arm Description
After screening/baseline evaluations, patients will be discharged home on moxonidine 0.2-0.4 mg/day PO. After two weeks, the patients will be re-admitted for study testing while on moxonidine. At completion of this testing, patients will start taking matching placebo once daily PO to be continued at home. After two, the patients will be re-admitted for study testing while on placebo.
Arm Title
Placebo then Moxonidine
Arm Type
Experimental
Arm Description
After screening/baseline evaluations, patients will be discharged home on placebo identical to moxonidine once daily PO. After two weeks, the patients will be re-admitted for study testing while on placebo. At completion of this testing, patients will start taking moxonidine 0.2-0.4 mg/day PO to be continued at home. After two weeks, the patients will be re-admitted for study testing while on moxonidine.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Other Intervention Name(s)
inactive pill
Intervention Description
Placebo pill identical to moxonidine administered for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Moxonidine Pill
Other Intervention Name(s)
Physiotens
Intervention Description
Moxonidine pill administered for 4 weeks
Primary Outcome Measure Information:
Title
Change in Orthostatic Symptom Burden [delta (delta VOSS)]
Description
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 4 weeks of placebo vs. moxonidine treatment.
Time Frame
after 30 min supine to after 15 min of 60 degrees upright tilt (delta VOSS), 2-3 hours after a dose of the treatment assigned for the previous period.
Secondary Outcome Measure Information:
Title
Change in Orthostatic Change in Heart Rate [delta (delta HR)]
Description
Difference in heart rate change from supine to upright postures (delta HR) following 4 weeks of placebo vs. moxonidine treatment [delta (delta HR)].
Time Frame
after 30 min supine to after 15 min of 60 degrees upright tilt (delta HR), 2-3 hours after a dose of the treatment assigned for the previous period.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
meets criteria for postural tachycardia syndrome (POTS)
a heart rate increase of ≥30 beats/min within 10 minutes of upright posture;
lack of orthostatic hypotension (blood pressure fall ≥ 20/10 mmHg within 3 minutes of standing); and
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 (days 5-13 of a 28-day cycle)
POTS with primary central sympathetic activation (psPOTS) as defined as having resting MSNA ≥ 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas Cayton, RN
Phone
(615) 875-6731
Email
autonomics@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
André Diedrich, MD, PhD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37221
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andre Diedrich, MD, PhD
Phone
615-343-6499
Email
autonomics@vumc.org
First Name & Middle Initial & Last Name & Degree
Thomas Cayton, RN
Phone
(615) 875-6731
Email
autonomics@vumc.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Autonomic Determinants of POTS - Pilot 2
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