Autonomic Determinants of POTS - Pilot1

NCT04050410 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: VANDERBILT_IRB_190703R56HL142583
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 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.

Conditions

Postural Tachycardia Syndrome

Keywords

postural tachycardia syndrome; hyperadrenergic; moxonidine; sympatholytic; orthostatic symptoms; POTS

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (1)

• Change in Orthostatic Change in Heart Rate [delta (delta HR)]

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

Study Arms (2)

Moxonidine

EXPERIMENTAL

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

Drug: Moxonidine

Placebo

PLACEBO COMPARATOR

Patients will receive a single oral dose of placebo.

Drug: Placebo

Interventions

Moxonidine DRUG

active drug given as 1 dose

Also known as: Physiotens

Moxonidine

Placebo DRUG

placebo pill given as 1 dose

Also known as: inactive pill

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Interventions

moxonidine

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Study Officials

• André Diedrich, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor of Medicine

Model Details: Randomized, double-blind, placebo-controlled crossover

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 8, 2019
• Study Start: August 27, 2019
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)