Moxonidine for Postural Orthostatic Tachycardia Syndrome (POTS)

Overseen By Andre Diedrich, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: Corticosteroids, NSAIDs, Statins, others

Disqualifiers: Pregnancy, Smoking, Diabetes, Hypertension, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Single dose administration

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Moxonidine to determine its effectiveness for people with Postural Orthostatic Tachycardia Syndrome (POTS), a condition that causes a high heart rate and other symptoms when standing. The researchers aim to discover if Moxonidine can reduce the impact of the nervous system's "fight or flight" response, potentially alleviating symptoms and improving quality of life for those affected. Participants will receive either Moxonidine or a placebo (a non-active pill) to compare results. The trial seeks individuals who have experienced POTS symptoms for at least six months without another known cause and who have an increased heart rate when standing. As an Early Phase 1 trial, this study focuses on understanding how Moxonidine works in people with POTS, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires participants to stop taking medications that affect autonomic function, blood pressure, or blood volume. If you are on such medications, you will need to withdraw from them to participate.

Is there any evidence suggesting that Moxonidine is likely to be safe for humans?

Research has shown that Moxonidine has been tested for safety and tolerability over eight years in numerous clinical trials. These trials include data from about 370,000 patient-years, providing a substantial amount of information. This extensive testing generally suggests that Moxonidine is well-tolerated, with most people not experiencing severe side effects.

In this study, researchers are examining Moxonidine for its potential to help with POTS, a condition characterized by a high heart rate and dizziness upon standing. Moxonidine is known to calm overactive nerves that control blood pressure and heart rate, which might alleviate these symptoms.

Since this trial is in the early stages, it is important to note that evidence is still being gathered about its safety specifically for POTS. However, the extensive history of Moxonidine use in other contexts provides some reassurance about its general safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for POTS?

Unlike the standard treatments for Postural Orthostatic Tachycardia Syndrome (POTS), which often involve beta-blockers or fludrocortisone, moxonidine acts via a different mechanism. Moxonidine is unique because it targets the central nervous system by activating imidazoline receptors, which may help better regulate blood pressure and heart rate. This novel approach could potentially offer a more targeted, efficient way to manage POTS symptoms, making it an exciting prospect for researchers looking for alternatives to current treatments.

What evidence suggests that Moxonidine might be an effective treatment for POTS?

Research has shown that Moxonidine, a medication that calms nerves controlling blood pressure and heart rate, might benefit people with Postural Orthostatic Tachycardia Syndrome (POTS). In this trial, participants will receive either Moxonidine or a placebo. Studies have found that Moxonidine can reduce symptoms like a high heart rate when standing, common in POTS patients. By lowering nervous system activity, it may improve the quality of life for those affected. There is ongoing interest in how this treatment could offer personalized relief for individuals with POTS. While more research is needed, early findings suggest it could be an effective treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

André Diedrich, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-55 with Postural Orthostatic Tachycardia Syndrome (POTS) characterized by a rapid heartbeat upon standing. Participants must have high resting sympathetic nerve activity, not be pregnant or severely overweight, and cannot be taking certain medications that affect autonomic function.

Inclusion Criteria

I have had symptoms when standing for 6 months without any other sudden illness causing it.

You are in the first half of your menstrual cycle, between days 5 and 13 of a 28-day cycle.

I have been diagnosed with a specific type of POTS based on nerve activity tests.

Exclusion Criteria

I am not currently taking oral corticosteroids, have no infections, and am not using NSAIDs.

I have a condition like heart disease, high blood pressure, I smoke, have high cholesterol, arthritis, or diabetes.

You have a body mass index (BMI) over 30.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of moxonidine or placebo to assess the effects on orthostatic symptoms and hemodynamics

Single dose administration

1 visit (in-person)

Observation

Participants are monitored for changes in heart rate and orthostatic symptom burden after administration

2-3 hours

Continuous monitoring during visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Moxonidine
• Placebo

Trial Overview The study tests the effect of Moxonidine, a blood pressure medication that reduces sympathetic nerve activity, on POTS symptoms compared to a placebo. The goal is to see if it can lower heart rate and improve symptoms when standing in patients with high sympathetic activity.

How Is the Trial Designed?

Group I: Moxonidine Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Patients will receive a single oral dose of placebo.

Moxonidine is already approved in European Union, Canada, China, Switzerland, United Kingdom for the following indications:

Approved in European Union as Physiotens for:

• Hypertension

Approved in Canada as Physiotens for:

• Hypertension

Approved in China as Moxonidine for:

• Hypertension

Approved in Switzerland as Physiotens for:

• Hypertension

Approved in United Kingdom as Physiotens for:

• Hypertension

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 4005 patients with hypertension, moxonidine significantly lowered blood pressure from an average of 168/97 mmHg to 141/83 mmHg over 8 weeks, with a response rate of 94% for all patients.

Moxonidine also contributed to a mean weight loss of 1.4 kg, particularly benefiting obese patients, while effectively managing blood pressure in those with metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study. Sharma, AM., Wagner, T., Marsalek, P.[2017]

Moxonidine, administered for two weeks at doses of 2 or 10 mg/kg, significantly reduced cardiac sympathetic tone in stroke-prone spontaneously hypertensive rats by 24.3% and 32.2%, respectively.

The treatment also improved cardiac baroreflex function, increasing the baroreflex gain in a dose-dependent manner, which suggests that moxonidine effectively modulates heart rate control mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of moxonidine on the cardiac chronotropic regulation in hypertensive rats SHR-SP]. Khokhlova, ON., Murashov, AN., Lavrova, LN., et al.[2014]

Moxonidine, an I1-imidazoline receptor agonist, effectively reduces blood pressure in both healthy volunteers and untreated hypertensives by decreasing muscle sympathetic nerve activity, indicating its potential as a treatment for hypertension.

In a study involving 25 hypertensive participants, moxonidine significantly lowered both systolic and diastolic blood pressure without affecting cholesterol levels, suggesting it may also be beneficial for other cardiovascular conditions associated with increased sympathetic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives. Wenzel, RR., Spieker, L., Qui, S., et al.[2019]

In a study of 32 patients with congestive heart failure, a single dose of moxonidine significantly reduced elevated plasma norepinephrine levels and produced a dose-dependent vasodilator response, leading to lower systemic and pulmonary arterial pressures.

Moxonidine was well tolerated and demonstrated substantial hemodynamic improvements, suggesting that further trials are warranted to assess its long-term efficacy in combination with standard CHF treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Dickstein, K., Manhenke, C., Aarsland, T., et al.[2019]

Moxonidine, a new antihypertensive agent, has a favorable safety profile with low rates of adverse effects, primarily dry mouth (8-9%) and somnolence (5-8%), over an extensive review of 74 clinical trials involving approximately 370,000 patient-years.

It effectively lowers blood pressure without exacerbating conditions like diabetes or chronic obstructive pulmonary disease, and its adverse effects tend to decrease with longer use, indicating it may be a valuable option for managing mild-to-moderate hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of moxonidine in the treatment of hypertension. Schachter, M., Luszick, J., Jäger, B., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04140721

NCT04140721 | Autonomic Determinants of POTS - Pilot 2 The primary outcome measure will be the difference in orthostatic symptom burden [delta (delta VOSS)] following 4 weeks of placebo vs. moxonidine treatment.

2. withpower.com withpower.com/trial/early-phase-1-tachycardia-7-2019-e5161

Moxonidine for Postural Orthostatic Tachycardia Syndrome ... This trial tests Moxonidine, a medication that calms overactive nerves controlling blood pressure and heart rate, on patients with POTS who have high nerve ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04050410

NCT04050410 | Autonomic Determinants of POTS - Pilot1 The primary outcome measure will be the difference in orthostatic symptom burden [delta (delta VOSS)] following placebo vs. moxonidine administration. after 30 ...

4. withpower.com withpower.com/trial/early-phase-1-syndrome-8-2021-3377b

Moxonidine for Postural Orthostatic Tachycardia Syndrome 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 ...

5. nhlbi.nih.gov nhlbi.nih.gov/sites/default/files/media/docs/NIH%20RTC%20on%20POTS_Final.signed.pdf

department of health and human services - NHLBI - NIH Postural orthostatic tachycardia syndrome (POTS) is a disabling condition in which standing produces a rapid heart rate, along with symptoms such as ...