Midodrine vs Abdominal Compression for Orthostatic Hypotension

Overseen By Andre Diedrich, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Pregnancy, Supine hypertension, Bedridden, others

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

Compensation: Varies

Number of Visits: 3

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of two treatments—abdominal compression and the medication midodrine—for individuals with orthostatic hypotension, a condition where blood pressure drops upon standing. Researchers seek to understand how these treatments impact heart and blood vessel health. Participants will try both treatments over approximately five days at Vanderbilt University Medical Center. Suitable candidates have experienced a drop in blood pressure when standing, associated with conditions like Parkinson's disease or autonomic failure. As an Early Phase 1 trial, this research focuses on understanding the treatments' effects in people, offering participants an opportunity to contribute to groundbreaking medical insights.

Will I have to stop taking my current medications?

The trial requires a medication withdrawal period, meaning you may need to stop taking certain medications. If you cannot tolerate this withdrawal, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that midodrine, a medication for low blood pressure, is generally safe but can cause some side effects. It improves blood pressure when standing, benefiting those with orthostatic hypotension (a drop in blood pressure upon standing). Some patients have reported mild side effects such as headaches, tingling on the scalp, and goosebumps.

Studies suggest that abdominal compression is a safe method for managing orthostatic hypotension. This involves wearing a tight garment around the abdomen to help raise blood pressure when standing. Research indicates it can increase standing blood pressure by about 10 mm Hg, which can be beneficial. Most people tolerate it well, though it might not be effective for everyone.

Overall, both treatments are considered quite safe, with side effects usually mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for orthostatic hypotension because they offer innovative approaches compared to standard care options like increased fluid intake, salt tablets, or other medications. Midodrine works by constricting blood vessels to raise blood pressure, offering a quick-acting solution that can be tailored with a single oral dose. On the other hand, abdominal compression provides a non-pharmacological option by applying pressure to the abdomen, potentially reducing blood pooling and improving blood flow with minimal side effects. Both treatments represent promising alternatives that could enhance patient comfort and effectiveness in managing symptoms.

What evidence suggests that this trial's treatments could be effective for orthostatic hypotension?

Research shows that midodrine, which participants in this trial may receive, can help treat orthostatic hypotension by improving blood pressure. Studies have found that it reduces symptoms like dizziness and lightheadedness more effectively than a placebo. Another group of participants in this trial will receive abdominal compression, a non-drug method. Research suggests this method can also raise blood pressure when standing, often by about 10 mm Hg. Both treatments are promising for managing orthostatic hypotension, but they work differently. ^{2 3 4 6 7}

Who Is on the Research Team?

Luis E Okamoto, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for men and women aged 40-80 with autonomic failure conditions like pure autonomic failure, multiple system atrophy, Parkinson's disease, or neurogenic orthostatic hypotension. Participants must experience a significant drop in blood pressure upon standing and be able to give informed consent. Pregnant individuals or those with certain health issues such as severe hypertension, recent surgeries, hernias, gastrointestinal reflux, fractures or implanted medical devices that could interfere with abdominal compression are excluded.

Inclusion Criteria

Patients who are willing and able to provide informed consent

I am between 40-80 years old with a diagnosis of autonomic failure, including conditions like pure autonomic failure, multiple system atrophy, or Parkinson's disease.

I experience a significant drop in blood pressure when standing, due to nerve issues.

Exclusion Criteria

I am bedridden or cannot stand due to severe health issues.

I do not have major lung, kidney, blood, liver diseases or other conditions that would stop me from completing the study.

You have had consistently high blood pressure while lying down.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment Day 1

Participants receive either midodrine with sham abdominal compression or abdominal compression with a placebo pill. Measurements of blood pressure, heart rate, and hemodynamic parameters are taken.

1 day

1 visit (in-person)

Treatment Day 2

Participants receive the alternate treatment from Day 1. Measurements of blood pressure, heart rate, and hemodynamic parameters are repeated.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 day

What Are the Treatments Tested in This Trial?

Interventions

• Abdominal Compression
• Midodrine

Trial Overview The study investigates the effects of midodrine (a medication) versus placebo pills and abdominal compression versus sham compression on cardiovascular risk markers in patients with low blood pressure when standing due to autonomic failure. Conducted over approximately five days at Vanderbilt University Medical Center, it includes screening and two testing days for each intervention.

How Is the Trial Designed?

Group I: Abdominal Compression Experimental Treatment 2 Interventions

Abdominal compression (up to 40 mmHg) combined with a placebo pill

Group II: Midodrine Active Control 2 Interventions

Single oral dose of midodrine (5-10mg) combined with sham abdominal compression

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

After short space-flights, orthostatic hypotension is linked to plasma volume depletion and activation of the Bezold-Jarisch reflex, which can cause fainting, while longer flights may lead to loss of cardiovascular reflex control similar to conditions seen in patients with autonomic failure.

Midodrine, an alpha-one agonist that causes blood vessel constriction without increasing heart rate, shows promise as a treatment for orthostatic hypotension after space flights and may help prevent vasovagal syncope, making it a potential adjunctive therapy for astronauts upon reentry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of postspace-flight orthostatic intolerance to vasovagal syncope and autonomic failure and the potential use of the alpha agonist midodrine for these conditions. Piwinski, SE., Jankovic, J., McElligott, MA.[2019]

In a study involving five male astronauts, the alpha-1 adrenergic agonist midodrine was administered after returning from space and did not cause any negative hemodynamic effects, indicating it is safe for use in this population.

Midodrine effectively protected against post-spaceflight increases in heart rate, suggesting it may be a beneficial countermeasure for astronauts experiencing orthostatic hypotension and presyncope upon return to Earth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of midodrine after spaceflight in astronauts without orthostatic hypotension. Platts, SH., Ziegler, MG., Waters, WW., et al.[2013]

In a study involving 67 patients with non-azotemic cirrhosis and tense ascites, midodrine treatment led to significant reductions in body weight and abdominal girth after 2 weeks, indicating its efficacy in managing symptoms of ascites.

The study was a randomized double-blind placebo-controlled trial, with 60 patients completing the study, which supports the safety and effectiveness of midodrine in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical study on the therapeutic role of midodrine in non azotemic cirrhotic patients with tense ascites: a double-blind, placebo-controlled, randomized trial. Ali, A., Farid, S., Amin, M., et al.[2016]

Mild abdominal compression (10mmHg) applied before standing can significantly reduce the drop in systolic blood pressure (SBP) associated with orthostatic hypotension in adults with neurogenic OH, showing a decrease of -50mmHg with a conventional binder and -46mmHg with an adjustable binder.

Increasing abdominal compression beyond mild levels while standing does not provide additional benefits and may worsen symptoms of orthostatic hypotension, indicating that moderate compression is optimal for managing blood pressure changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of patient-controlled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension. Figueroa, JJ., Singer, W., Sandroni, P., et al.[2018]

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, used for treating orthostatic hypotension, can lead to severe hypertension when the patient is lying down, particularly during general anesthesia.

A specific case is presented where a patient experienced significant hypertension while under anesthesia, highlighting the need for careful monitoring and preventive measures when using midodrine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supine hypertension during general anesthesia in a patient taking midodrine. Chaimberg, KH., Travis, KW.[2022]

Midodrine, an alpha1-adrenergic agonist, effectively prevented severe drops in blood pressure and heart function in a female astronaut experiencing post-spaceflight orthostatic hypotension after taking it post-flight.

This study suggests that midodrine could be a promising countermeasure for astronauts to manage orthostatic hypotension, indicating that reduced venous return may play a significant role in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine prescribed to improve recurrent post-spaceflight orthostatic hypotension. Platts, SH., Ziegler, MG., Waters, WW., et al.[2013]

Full-length compression therapy, which includes both the lower limbs and abdomen, is more effective than knee-length or thigh-length compression in reducing blood pressure drops associated with postural changes in patients with orthostatic hypotension.

Compression therapy, especially when it includes abdominal support, significantly improves symptoms of orthostatic hypotension, but the overall quality of evidence is low, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compression therapy in patients with orthostatic hypotension: a systematic review. Smeenk, HE., Koster, MJ., Faaij, RA., et al.[2018]

In a study of 1,010 ICU patients who were newly started on midodrine for hypotension, 67% continued the medication at ICU discharge, indicating its common use in managing blood pressure during recovery.

While midodrine use at ICU discharge was linked to shorter ICU stays and lower in-hospital mortality, it was also associated with a higher risk of 1-year mortality after hospital discharge, highlighting the need for careful monitoring and further research on its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuation of Newly Initiated Midodrine Therapy After Intensive Care and Hospital Discharge: A Single-Center Retrospective Study. Rizvi, MS., Nei, AM., Gajic, O., et al.[2020]

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/PMC11642223/

Current Landscape of Compression Products for Treatment ... Conclusions: The existing compression products do not fully meet needs of individuals with POTS or nOH, as evidenced by participant ratings on ...

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000005994

The efficacy of nonpharmacologic intervention for ... Abdominal compression was efficacious in 52% (95% CI 32.9–70.7) and improved standing SBP (+10 mm Hg [95% CI 2–18]). Compression stockings were the least ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02429557

Hemodynamic Mechanisms of Abdominal Compression in ... Study Overview. Compression garments have been shown to be effective in the treatment of orthostatic hypotension in autonomic failure patients.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0735109720379079

Compression Garment Reduces Orthostatic Tachycardia ... Abdominal and lower body compression reduced heart rate and improved symptoms during HUT in adult patients with POTS.

5. jacc.org jacc.org/doi/10.1016/j.jacc.2020.11.040

Compression Garment Reduces Orthostatic Tachycardia ... This study investigated the effectiveness of body compression to reduce orthostatic tachycardia and improve orthostatic symptoms in adults diagnosed with POTS.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11417920/

A Safety-Centric Study on the Use of Inflatable Abdominal ... The study focuses on the design and evaluation of inflatable abdominal binders for managing Orthostatic Hypotension.

7. mdpi.com mdpi.com/2077-0383/13/23/7304

Current Landscape of Compression Products for Treatment ... Conclusions: The existing compression products do not fully meet needs of individuals with POTS or nOH, as evidenced by participant ratings on multiple domains.