Midodrine for Low Blood Pressure

(SCI Trial)

Recruiting at 1 trial location

Overseen By Matt G. Maher, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: James J. Peters Veterans Affairs Medical Center

Disqualifiers: Psychiatric disorder, Stroke, Dementia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 visits

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Midodrine for low blood pressure?

Research shows that Midodrine is effective in increasing standing blood pressure and improving symptoms like dizziness and fatigue in patients with orthostatic hypotension (a condition where blood pressure drops when standing up). It is at least as effective as other similar drugs and is generally well-tolerated, although it can cause supine hypertension (high blood pressure when lying down) in some patients. ^{1 2 3 4 5}

Is midodrine generally safe for humans?

Midodrine is generally well tolerated, but it can cause side effects like piloerection (goosebumps), itching, and urinary retention. A significant concern is supine hypertension (high blood pressure when lying down), which can occur in up to 25% of patients and may persist even after stopping the medication. It's important to monitor blood pressure and adjust the dosage to minimize these risks. ^{1 2 3 5 6}

How does the drug midodrine differ from other treatments for low blood pressure?

Midodrine is unique because it is a short-acting drug that specifically targets alpha-adrenergic receptors to increase blood pressure in people who experience dizziness or fainting when standing up. Unlike some other treatments, it is well absorbed when taken orally and is effective without causing heart-related side effects, although it can lead to high blood pressure when lying down. ^{1 2 3 5 7}

What is the purpose of this trial?

The purpose of this study is to identify the effects of non-pharmacological and pharmacological anti-hypotensive treatment interventions on orthostatic hemodynamic responses, symptoms of autonomic dysreflexia and orthostatic hypotension, and levels of fatigue and comfort in hypotensive individuals with SCI.

Eligibility Criteria

This trial is for individuals with a spinal cord injury (SCI) that happened at least a year ago, affecting the C1-T6 regions of the spine. Participants must be non-ambulatory and have an AIS grade A, B, or C, indicating varying levels of impairment.

Inclusion Criteria

I have had a spinal cord injury due to trauma.

My spinal cord injury is classified as AIS A, B, or C.

It has been over a year since my injury.

Exclusion Criteria

I am currently experiencing a psychiatric disorder.

I have or might have cancer.

I have been diagnosed with Alzheimer's Disease or dementia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive non-pharmacological and pharmacological anti-hypotensive treatment interventions, including midodrine, droxidopa, and compression garments, over 6 laboratory visits

6 visits

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on orthostatic hemodynamics and symptoms

3 years

Treatment Details

Interventions

• Midodrine Hydrochloride

Trial Overview The study is testing Midodrine Hydrochloride to see how it affects blood pressure regulation in people with SCI who experience low blood pressure when they stand up (orthostatic hypotension).

Participant Groups

Group I: Study 2 Experimental Treatment 1 Intervention

Determine the effects of compression garments, midodrine, and droxidopa, compared to placebo, on orthostatic hemodynamics, symptoms of AD and OH and reporting of fatigue and thermal comfort.

Group II: Study 1 Experimental Treatment 1 Intervention

Twenty-five participants will be asked to visit the laboratory on 6 occasions, for an open-label, dose escalation trial to determine the effect of midodrine and droxidopa on supine and seated blood pressure and on symptoms of autonomic dysreflexia and orthostatic hypotension.

Midodrine Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as ProAmatine for:

• Orthostatic hypotension

Approved in European Union as Orvaten for:

• Orthostatic hypotension

Approved in Canada as Midodrine Hydrochloride for:

• Orthostatic hypotension

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Kessler Foundation

Collaborator

Trials

190

Recruited

11,300+

Findings from Research

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]

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]

Pyridostigmine bromide significantly improves standing blood pressure in patients with orthostatic hypotension (OH) without causing worsening of supine hypertension, based on a study involving 58 patients.

The treatment notably reduced the fall in standing diastolic blood pressure, indicating that it may enhance total peripheral resistance, which helps alleviate symptoms of OH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Singer, W., Sandroni, P., Opfer-Gehrking, TL., et al.[2018]

In a study involving 171 patients, midodrine significantly improved standing systolic blood pressure and reduced symptoms of lightheadedness in individuals with neurogenic orthostatic hypotension over a 6-week period.

Midodrine was found to be safe, with common side effects including pilomotor reactions, urinary retention, and supine hypertension, but overall it effectively alleviated symptoms and improved patient-reported outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. Low, PA., Gilden, JL., Freeman, R., et al.[2016]

Midodrine hydrochloride effectively stopped syncope attacks in a 10-year-old boy with severe orthostatic hypotension, demonstrating its efficacy as a treatment for this condition.

Despite its benefits, midodrine caused significant side effects, including supine hypertension, which persisted for 19 days after stopping the medication, highlighting the need for careful monitoring of patients after treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child. Olgar, S., Omeroglu, RE.[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]

In a double-blind, placebo-controlled study involving 19 patients with severe symptomatic orthostatic hypotension, midodrine significantly delayed the onset of syncopal symptoms compared to placebo, with an average difference of 521 seconds.

Midodrine was found to be well-tolerated, with only mild to moderate adverse events reported, none of which were deemed related to the medication, indicating its safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study. Smith, W., Wan, H., Much, D., et al.[2022]

References

1. 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]

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

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

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

Pyridostigmine treatment trial in neurogenic orthostatic hypotension. [2018]

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

Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. [2016]

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

Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child. [2018]

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

Supine hypertension during general anesthesia in a patient taking midodrine. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study. [2022]