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Autonomic Determinants of POTS - Pilot1

Primary Purpose

Postural Tachycardia Syndrome

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Moxonidine

Placebo

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

18 Years - 55 Years (Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

Vanderbilt University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Moxonidine

Placebo

Arm Description

Patients will receive a single oral dose of moxonidine 0.4 mg.

Patients will receive a single oral dose of placebo.

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 placebo vs. moxonidine administration.

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 placebo vs. moxonidine administration.

Full Information

NCT ID

NCT04050410

First Posted

August 2, 2019

Last Updated

February 14, 2023

Sponsor

Vanderbilt University Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT04050410

Brief Title

Autonomic Determinants of POTS - Pilot1

Official Title

Autonomic Determinants of Postural Tachycardia Syndrome (Acute Pilot Study 1)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 27, 2019 (Actual)

Primary Completion Date

July 31, 2024 (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

Data Monitoring Committee

Yes

5. Study Description

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.

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, placebo-controlled crossover

Masking

ParticipantInvestigator

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.

Allocation

Randomized

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Moxonidine

Arm Type

Experimental

Arm Description

Patients will receive a single oral dose of moxonidine 0.4 mg.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patients will receive a single oral dose of placebo.

Intervention Type

Drug

Intervention Name(s)

Moxonidine

Other Intervention Name(s)

Physiotens

Intervention Description

active drug given as 1 dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

inactive pill

Intervention Description

placebo pill given as 1 dose

Primary Outcome Measure Information:

Title

Change in Orthostatic Symptom Burden [delta (delta VOSS)]

Description

Time Frame

after 30 min supine to after 15 min upright (delta VOSS), 2-3 hours after placebo or moxonidine intake [delta (delta VOSS)].

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 placebo vs. moxonidine administration.

Time Frame

after 30 min supine to after 15 min upright (delta HR), 2-3 hours after placebo or moxonidine intake [delta (delta HR)].

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: female/male subjects, age 18-55 years, 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 10 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 (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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Vasile Urechie, MD

Phone

(615) 343-6499

autonomics@vumc.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

André Diedrich, MD

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

37232

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tomy Cayton, RN

Phone

615-875-6731

autonomics@vumc.org

First Name & Middle Initial & Last Name & Degree

Andre Diedrich, MD

12. IPD Sharing Statement

Plan to Share IPD

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