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

48 Participants Needed

Trial Summary

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.

What data supports the idea that Moxonidine for Postural Orthostatic Tachycardia Syndrome is an effective drug?

The available research does not provide any data on the effectiveness of Moxonidine for Postural Orthostatic Tachycardia Syndrome. The studies mentioned focus on other treatments like low-dose naltrexone and propranolol, but not Moxonidine. Therefore, there is no evidence from the provided information to support the idea that Moxonidine is an effective treatment for this condition. ^{1 2 3 4 5}

What safety data is available for moxonidine?

Moxonidine has been evaluated for safety and tolerability over an 8-year period in 74 clinical trials with an estimated 370,000 patient-years of exposure. Common adverse effects include dry mouth, somnolence, headache, and dizziness, with serious adverse events being rare. The incidence of adverse effects decreases with prolonged use. Moxonidine does not exacerbate conditions like diabetes or COPD and does not interact significantly with medications like hydrochlorothiazide, digoxin, and glibenclamide. Post-marketing surveillance identified additional adverse effects such as nausea and allergic skin reactions. ^{6 7 8 9 10}

Is moxonidine safe for human use?

Moxonidine has been studied for safety in humans, primarily for treating high blood pressure. Common side effects include dry mouth, sleepiness, headache, and dizziness, but serious side effects are rare. It has been used safely in many patients over several years, and its side effects tend to decrease with continued use. ^{6 7 8 9 10}

Is the drug Moxonidine a promising treatment for Postural Orthostatic Tachycardia Syndrome?

Moxonidine is a promising drug because it effectively lowers blood pressure and heart rate by reducing the activity of the sympathetic nervous system. It also improves metabolic health, is well tolerated, and can be taken once daily. These benefits suggest it could be helpful for conditions like Postural Orthostatic Tachycardia Syndrome, which involves issues with heart rate and blood pressure. ^{6 11 12 13 14}

How does the drug moxonidine differ from other treatments for Postural Orthostatic Tachycardia Syndrome?

Moxonidine is unique because it works by activating specific receptors in the brain called I1-imidazoline receptors, which helps reduce the activity of the sympathetic nervous system, leading to lower blood pressure and heart rate. This central action is different from many other treatments that may not target these specific receptors or have the same effect on sympathetic nerve activity. ^{6 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

André Diedrich, MD, PhD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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, 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, 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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Low-Dose Naltrexone Use in Postural Orthostatic Tachycardia Syndrome: A Case Series. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Utilisation of medications to reduce symptoms in children with postural orthostatic tachycardia syndrome. [2019]

3. United States 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. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and tolerability of moxonidine in the treatment of hypertension. [2018]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effect of moxonidine on the cardiac chronotropic regulation in hypertensive rats SHR-SP]. [2014]

9. England pubmed.ncbi.nlm.nih.gov

Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Hemodynamic and neurohumoral effects of moxonidine in patients with essential hypertension. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Pharmacology of moxonidine, an I1-imidazoline receptor agonist. [2019]

12. Germany pubmed.ncbi.nlm.nih.gov

General pharmacology of the novel centrally acting antihypertensive agent moxonidine. [2014]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Moxonidine: a review of its use in essential hypertension. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. [2019]