Autonomic Determinants of POTS - Pilot 2

NCT04140721 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: VANDERBILT_IRB_191749R01HL142583
• 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. 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.

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 4 weeks of placebo vs. moxonidine treatment.

  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 Outcomes (1)

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

  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.

Study Arms (2)

Moxonidine then Placebo

EXPERIMENTAL

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.

Drug: Placebo oral tablet; Drug: Moxonidine Pill

Placebo then Moxonidine

EXPERIMENTAL

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.

Drug: Placebo oral tablet; Drug: Moxonidine Pill

Interventions

Placebo oral tablet DRUG

Placebo pill identical to moxonidine administered for 4 weeks

Also known as: inactive pill

Moxonidine then Placebo; Placebo then Moxonidine

Moxonidine Pill DRUG

Moxonidine pill administered for 4 weeks

Also known as: Physiotens

Moxonidine then Placebo; Placebo then Moxonidine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

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, 37221, 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, PhD

  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: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor of Medicine

Model Details: randomized, double blind, crossover design

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 28, 2019
• Study Start: August 31, 2021
• 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)