Autonomic Determinants of POTS - Pilot1

NCT ID: NCT04050410

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-27
• Study Completion Date: 2025-12-31

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.

Conditions

Postural Tachycardia Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Moxonidine

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

Group Type: EXPERIMENTAL

Moxonidine

Intervention Type: DRUG

active drug given as 1 dose

Placebo

Patients will receive a single oral dose of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo pill given as 1 dose

Interventions

Moxonidine

active drug given as 1 dose

Intervention Type: DRUG

Placebo

placebo pill given as 1 dose

Intervention Type: DRUG

Other Intervention Names

Physiotens; inactive pill

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Andre' Diedrich

Research Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

André Diedrich, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

R56HL142583

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VANDERBILT_IRB_190703

Identifier Type: -

Identifier Source: org_study_id