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

Trial Summary

What is the purpose of this trial?

The objective of this study is to find a more objective and accurate way to assess the efficacy of the treatment for neurogenic orthostatic hypotension. For this purpose, the investigators will use an activity monitor to determine the amount of time patients spend in the upright position (standing and walking; upright time) during 1 week of placebo (a pill with no active ingredients) and 1 week of their regular medication for orthostatic hypotension (midodrine or atomoxetine at their usual doses). Total upright time (i.e. tolerance to standing and walking) will be compared between placebo and active treatment to test the hypothesis that it can be used to assess the efficacy of the treatment for orthostatic hypotension and whether this outcome is superior to the assessment of symptoms using validated questionnaires.

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 data supports the effectiveness of the drug Midodrine for treating neurogenic orthostatic hypotension?

Research shows that Midodrine significantly increases standing blood pressure and improves symptoms like dizziness and light-headedness in patients with orthostatic hypotension. It is considered effective and well-tolerated, with fewer side effects compared to other similar drugs. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Midodrine is generally well-tolerated, with common mild side effects like goosebumps, itching, and tingling. However, it can cause high blood pressure when lying down in up to 25% of patients, which can be managed by adjusting the timing of doses. ^{1 2 3 5 6}

How does the drug used in this trial differ from other treatments for neurogenic orthostatic hypotension?

Atomoxetine, used in this trial, is unique because it blocks the norepinephrine transporter, which can increase blood pressure in patients with some remaining sympathetic activity, especially when standing. This differs from midodrine, which directly causes blood vessels to constrict, and may make atomoxetine more effective in improving symptoms when upright. ^{1 5 7 8 9}

Research Team

Italo Biaggioni, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. [2019]

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

Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. [2018]

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

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

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

Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension. [2022]

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

Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. [2021]

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

Trends in Use of Midodrine in the ICU: A Single-Center Retrospective Case Series. [2019]

7. Austria pubmed.ncbi.nlm.nih.gov

Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms. [2020]

8. Italy pubmed.ncbi.nlm.nih.gov

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

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

A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. [2019]