Moxonidine for Postural Orthostatic Tachycardia Syndrome

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Moxonidine can reduce symptoms for people with Postural Orthostatic Tachycardia Syndrome (POTS). POTS can cause a high heart rate and other uncomfortable symptoms when standing. Researchers aim to determine if Moxonidine, which calms the part of the nervous system responsible for these symptoms, might be an effective treatment. Participants will take either Moxonidine or a placebo (a harmless pill with no active drug) in different sequences. This trial suits those with POTS who experience symptoms when standing and have a specific type of nervous system activity. As an Early Phase 1 trial, this research focuses on understanding how Moxonidine works in people, offering participants a chance to contribute to groundbreaking treatment insights.

Do I have to stop taking my current medications for this trial?

Yes, you must stop taking medications that affect autonomic function, blood pressure, or blood volume to participate in this trial.

Will I have to stop taking my current medications?

Yes, you will need to stop taking medications that affect autonomic function, blood pressure, or blood volume to participate in this trial.

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

Research has shown that Moxonidine has been studied for safety and long-term tolerability. Researchers tested it in 74 clinical trials over 8 years, covering approximately 370,000 patient-years of use. This extensive use has provided a wealth of information about its effects on people.

Although specific side effects are not listed here, the substantial data suggests that Moxonidine is generally well-tolerated. This strong safety record from past use is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Moxonidine is unique because it targets the sympathetic nervous system, which is different from the usual medications for Postural Orthostatic Tachycardia Syndrome (POTS) like beta-blockers, fludrocortisone, or midodrine. Unlike these standard treatments, which often focus on managing heart rate or blood volume, moxonidine reduces sympathetic nerve activity by acting on central imidazoline receptors. This could potentially offer a more direct approach to addressing the underlying autonomic dysfunction in POTS. Researchers are excited about moxonidine because it might provide a new avenue for relief, especially for patients who don't respond well to existing therapies.

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

Research has shown that Moxonidine can reduce nerve activity, which is often high in people with Postural Orthostatic Tachycardia Syndrome (POTS). This high activity may cause symptoms like a rapid heartbeat when standing. Moxonidine has shown promise in lowering heart rate and improving these symptoms. In this trial, participants will receive either Moxonidine or a placebo in different sequences. Similar studies have demonstrated that patients experienced fewer symptoms when standing after taking Moxonidine compared to a placebo. These findings suggest that Moxonidine could help manage POTS symptoms by calming the nerves that control blood pressure and heart rate. ^{1 2 3 5 6}

Who Is on the Research Team?

André Diedrich, MD, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for young women with POTS, a condition causing rapid heartbeat when standing. Participants must have had symptoms for at least 6 months, experience a heart rate increase of ≥30 bpm within 10 minutes of standing without significant blood pressure drops, and be in the early phase of their menstrual cycle. They should not be overweight or suffering from conditions like heart disease, high blood pressure, diabetes, or taking certain medications.

Inclusion Criteria

Able and willing to provide informed consent

I have been diagnosed with postural tachycardia syndrome (POTS).

You are in the first half of your menstrual cycle.

Exclusion Criteria

I cannot stop taking my medication that affects my blood pressure or heart function.

You have a body mass index (BMI) higher than 30.

I have a condition like heart disease, high blood pressure, or diabetes, or I'm currently taking certain medications like steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation

Baseline evaluations are conducted before starting the treatment phase

1 week

1 visit (in-person)

Treatment

Participants receive either placebo or moxonidine for 2 weeks, followed by crossover to the other treatment for another 2 weeks

4 weeks

2 visits (in-person) for study testing after each 2-week period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Moxonidine
• Placebo oral tablet

Trial Overview The study tests Moxonidine's effect on POTS symptoms compared to a placebo. Moxonidine is a blood pressure medication that reduces sympathetic nerve activity which might help lower heart rate and improve standing tolerance in patients with high resting sympathetic activity.

How Is the Trial Designed?

Group I: Placebo then Moxonidine Experimental Treatment 2 Interventions

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.

Group II: Moxonidine then Placebo Experimental Treatment 2 Interventions

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.

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

Moxonidine effectively lowers blood pressure in patients with mild to moderate hypertension, showing similar efficacy to first-line antihypertensive medications when used alone or in combination with other treatments.

It is particularly beneficial for patients with hypertension and metabolic issues, as it improves metabolic profiles, is well tolerated, and has a low risk of drug interactions, making it suitable for once-daily administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxonidine: a review of its use in essential hypertension. Fenton, C., Keating, GM., Lyseng-Williamson, KA.[2018]

Moxonidine effectively lowers blood pressure by activating I1-imidazoline receptors in the brain, leading to reduced sympathetic nervous system activity, as demonstrated in various animal models of hypertension.

In addition to its antihypertensive effects, moxonidine shows potential benefits such as improving glucose metabolism, increasing urine flow, and lowering intraocular pressure, suggesting it may have protective effects beyond just reducing blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of moxonidine, an I1-imidazoline receptor agonist. Ziegler, D., Haxhiu, MA., Kaan, EC., et al.[2019]

In a case series of six patients with postural orthostatic tachycardia syndrome (POTS) treated with low-dose naltrexone (LDN), three patients reported improvement in their symptoms, while two discontinued treatment due to lack of perceived benefit.

LDN demonstrated a favorable safety profile with no reported side effects, but the overall efficacy remains unclear, as patient-reported outcomes showed inconsistent changes, highlighting the need for larger, high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Naltrexone Use in Postural Orthostatic Tachycardia Syndrome: A Case Series. Stallkamp Tidd, SJ., Cantrell, C., Greene, BD., et al.[2023]

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, 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]

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]

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]

A single oral dose of 0.4 mg moxonidine significantly reduced blood pressure in patients with essential hypertension, decreasing from 176/105 mmHg to 158/95 mmHg over 4 hours, while systemic vascular resistance also decreased significantly.

Moxonidine was well tolerated and led to favorable changes in neurohumoral factors, including a significant reduction in plasma levels of noradrenaline and renin, indicating its potential effectiveness as an antihypertensive agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic and neurohumoral effects of moxonidine in patients with essential hypertension. Mitrovic, V., Patyna, W., Hüting, J., et al.[2019]

In a meta-analysis of 6 studies involving 783 patients with neurogenic orthostatic hypotension, both droxidopa and midodrine significantly increased standing systolic blood pressure (sSBP) compared to placebo, with midodrine showing a greater increase (17 mm Hg) than droxidopa (6.2 mm Hg).

While both medications improved sSBP, midodrine was associated with a significantly higher risk of supine hypertension compared to placebo, indicating that droxidopa may be a safer option for patients concerned about this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials. Chen, JJ., Han, Y., Tang, J., et al.[2019]

In a study involving 54 patients with POTS, low-dose propranolol (20 mg) significantly reduced heart rates and improved symptoms compared to placebo, indicating its efficacy as a treatment option.

Higher doses of propranolol (80 mg) resulted in greater reductions in heart rate but did not provide additional symptom relief and may have worsened symptoms, suggesting that lower doses may be more beneficial for managing POTS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Raj, SR., Black, BK., Biaggioni, I., et al.[2021]

Postural orthostatic tachycardia syndrome (POTS) is a common cause of dizziness in young people, often misdiagnosed as anxiety due to its symptoms, which can lead to years of undiagnosed issues.

The paper discusses various treatment strategies for POTS, including both conservative and pharmacologic approaches, while also exploring the condition's complex cardiovascular mechanisms and the physiological basis of heart rate variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postural Orthostatic Tachycardia Syndrome Misdiagnosed as Anxiety: A Case Report with a Review of Therapy and Pathophysiology. Kesserwani, H.[2020]

Moxonidine effectively reduces blood pressure and heart rate in various animal models of hypertension, indicating its potential as a treatment for high blood pressure.

The drug's hypotensive effect is primarily mediated through central nervous system action, specifically by stimulating presynaptic alpha 2-adrenoceptors, which allows for a greater separation between its therapeutic effects and side effects compared to similar medications like clonidine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General pharmacology of the novel centrally acting antihypertensive agent moxonidine. Armah, BI., Hofferber, E., Stenzel, W.[2014]

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]

In a study of 708 patients with postural orthostatic tachycardia syndrome, various medications were found to effectively manage symptoms, with success rates of 52.2% for light-headedness and 53.4% for pain.

The study highlighted that while insomnia treatment was more effective in females, other symptom therapies showed no gender differences, indicating that medications can be tailored to individual symptoms for better management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilisation of medications to reduce symptoms in children with postural orthostatic tachycardia syndrome. Boris, JR., Bernadzikowski, T.[2019]

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. ctv.veeva.com ctv.veeva.com/study/autonomic-determinants-of-pots-pilot1

Autonomic Determinants of POTS - Pilot1 - ClinicalTrials.Veeva Moxonidine lowers sympathetic activity. The investigators believe patients with high resting sympathetic activity might benefit from Moxonidine.

6. 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 ...