Accelerometer Monitoring for Neurogenic Orthostatic Hypotension

Overseen By Jinwoo Park, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must be taking: Midodrine, Atomoxetine

Must not be taking: Anticoagulants

Disqualifiers: Diabetes, Amyloidosis, Coronary artery disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for measuring the effectiveness of treatments for neurogenic orthostatic hypotension, a condition that causes a drop in blood pressure when standing. Participants will wear an activity monitor for two weeks to track their daily standing and walking duration. The trial compares a placebo pill with regular medication (either midodrine or atomoxetine) to determine which better improves the ability to stay upright. Individuals with conditions like Parkinson's disease or Multiple Systems Atrophy who still experience symptoms despite treatment may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future treatment strategies.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medication for neurogenic orthostatic hypotension, as it involves comparing your regular medication (midodrine or atomoxetine) with a placebo. However, you should not be taking more than one medication for this condition, except for pyridostigmine or fludrocortisone, which are allowed.

What prior data suggests that this accelerometer is safe for monitoring neurogenic orthostatic hypotension?

Research has shown that both midodrine and atomoxetine are generally safe and effective for treating neurogenic orthostatic hypotension, a condition where blood pressure drops upon standing. One study found that midodrine was effective for individuals with moderate-to-severe cases and was well-tolerated. Another study demonstrated that atomoxetine improved blood pressure and was safe for short-term use.

Comparisons of both treatments have found them effective, with atomoxetine sometimes yielding slightly better results. Patients taking these medications usually do not experience serious side effects, although midodrine is not recommended for those with certain kidney issues. Overall, existing evidence supports the safety of both medications for this condition. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments midodrine and atomoxetine for neurogenic orthostatic hypotension because they're exploring different ways to manage this condition. Midodrine works by constricting blood vessels to help maintain blood pressure, while atomoxetine, typically used for ADHD, has a unique mechanism that increases norepinephrine levels, which may help stabilize blood pressure when standing. These approaches offer potential alternatives to the standard care options, which often focus on dietary changes and compression garments, by directly addressing the underlying blood pressure issues with medication.

What evidence suggests that using an accelerometer is effective for assessing treatment efficacy in neurogenic orthostatic hypotension?

Research has shown that midodrine, one of the treatments in this trial, can greatly improve symptoms of neurogenic orthostatic hypotension. Studies have found that it raises blood pressure when standing and reduces symptoms like dizziness and tiredness. One study found that midodrine was more effective than a placebo in easing these symptoms.

Atomoxetine, another treatment option in this trial, has also proven effective for neurogenic orthostatic hypotension. It increases blood pressure when standing and reduces related symptoms. Some research even suggests that atomoxetine might work better than midodrine for certain patients. Both treatments have shown promise in improving the quality of life for people with this condition. ^{1 3 6 7 8}

Who Is on the Research Team?

Italo Biaggioni, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for people aged 40-80 with conditions like Multiple Systems Atrophy, Pure Autonomic Failure, or Parkinson's disease who have low blood pressure upon standing. They must be on midodrine or atomoxetine treatment and not bedridden, pregnant, or have had recent major cardiovascular events.

Inclusion Criteria

Able and willing to provide informed consent

I can stay with my caregiver during the study.

I may have a condition like MSA, PAF, or Parkinson's with low blood pressure when standing.

Exclusion Criteria

Pregnancy

I am on multiple medications for low blood pressure when standing, but not more than pyridostigmine or fludrocortisone.

I have a condition like diabetes that affects my nerves.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two separate weeks of treatment: one week with placebo and one week with their regular medication (midodrine or atomoxetine), with a one-week washout period in between.

3 weeks

Home-based with caregiver assistance and oversight from the investigative team

Follow-up

Participants are monitored for safety and effectiveness after treatment using questionnaires and blood pressure measurements.

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Accelerometer
• Midodrine or atomoxetine pill
• Placebo

Trial Overview The study tests if an accelerometer can better measure the effectiveness of treatments for neurogenic orthostatic hypotension compared to questionnaires. Participants will take either their regular medication or a placebo pill while wearing the activity monitor.

How Is the Trial Designed?

Group I: placebo Experimental Treatment 2 Interventions

Placebo pill will be taken for 7 days at the same frequency as their regular treatment with either midodrine or atomoxetine.

Group II: Standard treatment Active Control 2 Interventions

Either midodrine or atomoxetine at their regular dose.

Midodrine or atomoxetine pill is already approved in United States, European Union for the following indications:

Approved in United States as ProAmatine for:

• Orthostatic hypotension

Approved in European Union as Orvaten for:

• Orthostatic hypotension

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Abdominal binders are strongly recommended as a non-pharmacological measure for managing neurogenic orthostatic hypotension, highlighting the importance of patient education and lifestyle adjustments.

For pharmacological treatment, midodrine and droxidopa are strongly recommended due to their safety and efficacy, while other alternative medications have weaker recommendations and lower quality evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms. Eschlböck, S., Wenning, G., Fanciulli, A.[2020]

Oral midodrine effectively increases standing systolic blood pressure and improves symptoms of orthostatic hypotension, such as dizziness and light-headedness, making it a valuable treatment option for this condition.

Midodrine is well tolerated with common side effects including piloerection and urinary retention, and the risk of supine hypertension can be managed by timing the last dose appropriately, enhancing its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. McClellan, KJ., Wiseman, LR., Wilde, MI.[2018]

In a double-blind study involving 8 patients with refractory orthostatic hypotension, midodrine significantly improved standing blood pressure and the ability to stand compared to ephedrine, which showed no significant effect.

Midodrine was found to be safe and effective in increasing both systolic and diastolic blood pressure in standing positions, while ephedrine did not provide a significant benefit over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. Fouad-Tarazi, FM., Okabe, M., Goren, H.[2019]

In a study involving 25 patients with neurogenic orthostatic hypotension (NOH), midodrine significantly increased standing systolic blood pressure, with the most effective doses being 10 mg and 20 mg, showing a clear dose-response relationship.

The optimal dosing strategy for midodrine is 10 mg taken two to three times daily, which effectively improves symptoms of NOH and maintains a peak blood pressure increase approximately one hour after administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Wright, RA., Kaufmann, HC., Perera, R., et al.[2019]

In a study involving 65 patients with severe autonomic failure, atomoxetine was found to significantly increase upright systolic blood pressure by an average of 7.5 mm Hg compared to midodrine, which did not show a similar effect.

Atomoxetine also improved orthostatic hypotension-related symptoms more effectively than midodrine, suggesting it may be a better treatment option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Ramirez, CE., Okamoto, LE., Arnold, AC., et al.[2021]

In a multicenter study involving 97 patients with neurogenic orthostatic hypotension, midodrine significantly increased standing systolic blood pressure, particularly showing a 27% increase at the 10 mg dose for the Bradbury Eggleston syndrome subgroup.

Midodrine not only improved blood pressure but also alleviated symptoms like fainting and blurred vision, with mild side effects, confirming its safety and efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine in neurogenic orthostatic hypotension. A new treatment. Gilden, JL.[2013]

Midodrine effectively increases standing blood pressure and alleviates symptoms of orthostatic hypotension, such as weakness and fatigue, without causing cardiac stimulation, making it a safe option for patients.

In comparative studies, midodrine demonstrated at least equal efficacy to other sympathomimetic agents while causing fewer severe side effects, suggesting it is a preferable choice for managing hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders. McTavish, D., Goa, KL.[2018]

In a study involving 87 patients with neurogenic orthostatic hypotension, treatments with midodrine, pyridostigmine, or their combination significantly improved blood pressure drops and symptoms over a 3-month period.

Midodrine alone was found to be more effective than pyridostigmine alone in alleviating orthostatic symptoms, and the treatment was generally safe with only mild to moderate adverse events reported in 11.5% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension. Byun, JI., Moon, J., Kim, DY., et al.[2022]

Midodrine, an oral alpha-agonist, significantly reduced the need for vasopressors in ICU patients, with a decrease from 663 to 344 patients on vasopressors 24 hours after initiation, indicating its efficacy in managing hypotension.

The most common side effect observed was asymptomatic bradycardia in 172 patients, highlighting a safety concern, while two cases of bowel ischemia were reported, suggesting the need for careful monitoring when using midodrine in the ICU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in Use of Midodrine in the ICU: A Single-Center Retrospective Case Series. Rizvi, MS., Trivedi, V., Nasim, F., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9982187/

Effects of Atomoxetine for the Treatment of Neurogenic ... Several previous studies have found that a daily atomoxetine dose of 18 mg was effective in relieving orthostatic BP decrease and OH-related symptoms in ...

2. ahajournals.org ahajournals.org/doi/10.1161/hyp.79.suppl_1.P063

Abstract P063: Long-term Efficacy Of Atomoxetine For The ... We previously reported that atomoxetine, a norepinephrine transporter inhibitor, acutely improved upright blood pressure and symptoms in NOH, mostly in ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39294522/

Atomoxetine on neurogenic orthostatic hypotension We aimed to evaluate the effect of atomoxetine over four weeks in patients with nOH.

4. link.springer.com link.springer.com/article/10.1007/s10286-024-01051-2

Atomoxetine on neurogenic orthostatic hypotension Further, we reported that a single atomoxetine dose resulted in higher standing BP increases and more pronounced symptomatic reductions as ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03350659

Efficacy and Safety of Midodrine and Atomoxetine for ... Secondary end-points were improvement in orthostatic blood pressure (BP) drop at 1 and 3 months. Detailed Description. Visit 1. Enroll, baseline evaluation of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11543771/

Atomoxetine on neurogenic orthostatic hypotension During the optimization phase, 11 responded to 10 mg and 38 responded to 18 mg atomoxetine; atomoxetine significantly improved standing BP acutely (20 ± 22.6) ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/acn3.50968

Efficacy of atomoxetine versus midodrine for neurogenic ... One-month atomoxetine treatment was effective and safe in nOH patients. Atomoxetine improved orthostatic BP changes as much as midodrine and was ...

8. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.118.11790

Synergistic Pressor Effect of Atomoxetine and ... Our results showed that the combination of atomoxetine and pyridostigmine elicited a profound and synergistic effect on seated BP in severe ...