Midodrine for Low Blood Pressure

(SCI Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: James J. Peters Veterans Affairs Medical Center

Disqualifiers: Psychiatric disorder, Stroke, Dementia, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

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.

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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).

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

James J Peters VA Medical Center Bronx, NY

Kessler Foundation West Orange, NJ

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center Lead Sponsor

Kessler Foundation Collaborator

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] Midodrine, a peripheral alpha-adrenergic agonist, finds use in the clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies. Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine. In patients with refractory orthostatic hypotension oral midodrine increases standing blood pressure and improves symptoms of orthostatism, such as weakness, syncope, blurred vision and fatigue, without any associated cardiac stimulation. Comparative studies have shown midodrine to be clinically at least as effective as other sympathomimetic agents (norfenefrine, etilefrine, dimetofrine and ephedrine) and dihydroergotamine in this regard. Additionally, midodrine appears to cause less frequent and severe adverse effects associated with alpha-receptor agonism such as piloerection and urinary hesitancy. The most commonly experienced adverse effects--piloerector reactions, gastrointestinal disorders, and cardiovascular complaints--are generally mild and can be controlled by reducing the dosage of midodrine. Thus, midodrine is at least as useful as other currently available options in the management of orthostatic or secondary hypotension, and represents a stepping stone towards optimal therapy.

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

Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. [2018] Midodrine is a prodrug which undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration. Oral midodrine significantly increases 1-minute standing systolic blood pressure compared with placebo. The drug also improves standing time and energy level and clinical symptoms of orthostatic hypotension including dizziness, light-headedness and syncope. Comparative studies have shown midodrine to have similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension. Midodrine is well tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention and chills. The risk of supine hypertension, which is associated with midodrine therapy in up to 25% of patients, can be reduced by taking the final daily dose at least 4 hours before bedtime. Thus, oral midodrine is an effective therapeutic option for the management of various forms of orthostatic hypotension. This well-tolerated agent is likely to be useful in conjunction with standard nonpharmacological care.

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

Pyridostigmine treatment trial in neurogenic orthostatic hypotension. [2018] Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension.

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] To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an alpha-agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone.

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

Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child. [2018] Midodrine hydrochloride is a potent peripherally-acting alpha1 agonist that is well absorbed and rapidly metabolized to its active metabolite. It has been used for the treatment of refractory syncope but has the important side effect of supine hypertension. A 10-year-old boy with severe symptomatic orthostatic hypotension was treated with midodrine. After therapy, syncope attacks ceased but he suffered nighttime headaches, nausea, transient rash and itchy/prickly scalp. Midodrine was discontinued when supine hypertension was noticed. However, his supine hypertension continued until day 19 after discontinuation. This case shows that patients receiving midodrine should be observed for supine hypertension for a prolonged period.

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

Supine hypertension during general anesthesia in a patient taking midodrine. [2022] Midodrine, a drug used to treat symptomatic orthostatic hypotension, may cause or exacerbate supine hypertension. We describe a case of a patient taking midodrine who exhibited severe hypertension during general anesthesia. Possible preventive measures to avoid this complication are discussed.

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] Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension. The US Food and Drug Administration's Subpart H approval, under which midodrine was initially approved, requires post-marketing studies to confirm midodrine's clinical benefit in this indication. The purpose of this study was to evaluate the clinical benefit of midodrine with regard to symptom response.