Accelerometer Monitoring for Neurogenic Orthostatic Hypotension
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
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
Approved in 2 Jurisdictions
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?
Is the treatment generally safe for humans?
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.15789
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.
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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.
See 4 more
Trial 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 (Other)
- Midodrine or atomoxetine pill (Other)
- Placebo (Other)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: placeboExperimental Treatment2 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 treatmentActive Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Autonomic Dysfunction Center/ Vanderbilt University Medical CenterNashville, TN
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Who Is Running the Clinical Trial?
Vanderbilt University Medical CenterLead Sponsor
References
Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. [2019]In this double-blind study, the authors compared the safety and efficacy of the investigational oral agent midodrine, a specific alpha 1-sympathomimetic agent, with ephedrine, a nonspecific alpha- and beta-adrenergic receptor agonist. Eight patients (4 men and 4 women) with refractory orthostatic hypotension resulting from autonomic failure were studied. This study was based on the notion that neurogenic orthostatic hypotension results from attenuation of adrenergic nerve traffic and not from alpha-adrenergic receptor dysfunction. Although arteriolar vasoconstrictors seem to be appropriate therapeutic agents, their success has been limited, and the search for an ideal drug is ongoing.
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.
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.
Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension. [2022]To evaluate the long-term (for up to 3 months) efficacy and safety of single or combined therapy with midodrine and pyridostigmine for neurogenic orthostatic hypotension (OH).
Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. [2021]The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.
Trends in Use of Midodrine in the ICU: A Single-Center Retrospective Case Series. [2019]Midodrine is an oral alpha-agonist approved for orthostatic hypotension. The use of midodrine as a vasopressor sparing agent has steadily increased in the ICU despite limited evidence for its safety in that setting. We describe the trends in use and reported side effects and complications of midodrine in multidisciplinary ICUs of a tertiary care institution.
Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms. [2020]Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced hypotension are common features of cardiovascular autonomic failure. Despite the serious impact on patient's quality of life, evidence-based guidelines for non-pharmacological and pharmacological management are lacking at present. Here, we provide a systematic review of the literature on therapeutic options for neurogenic orthostatic hypotension and related symptoms with evidence-based recommendations according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Patient's education and non-pharmacological measures remain essential, with strong recommendation for use of abdominal binders. Based on quality of evidence and safety issues, midodrine and droxidopa reach a strong recommendation level for pharmacological treatment of neurogenic orthostatic hypotension. In selected cases, a range of alternative agents can be considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation strength is weak and quality of evidence is low (atomoxetine, octreotide) or very low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin). In case of severe postprandial hypotension, acarbose and octreotide are recommended (strong recommendation, moderate level of evidence). Alternatively, voglibose or caffeine, for which a weak recommendation is available, may be useful.
Midodrine in neurogenic orthostatic hypotension. A new treatment. [2013]Neurogenic orthostatic hypotension is a severely disabling condition due to deficient peripheral vasoconstrictor tone in response to the upright position and is characterized by a decrease in blood pressure upon standing associated with symptoms of lightheadedness, dizziness, visual "white-out", weakness, lack of energy, near syncope or even syncope. Previous pharmacologic treatment of neurogenic orthostatic hypotension has been problematic. Midodrine, a new specific alpha-1-agonist has been shown to produce arteriolar constriction and decrease in venous pooling via a constriction of venous capacitance vessels. Therefore, a recent multicenter study evaluated the safety and efficacy of midodrine therapy in 97 patients with neurogenic orthostatic hypotension due to various etiologies: Shy Drager syndrome (No. 18); Bradbury Eggleston syndrome (idiopathic orthostatic hypotension) (No. 20); diabetic autonomic neuropathy (No. 27); Parkinson's disease (No. 22); and miscellaneous (No. 10). Following one week of placebo therapy, the patients were randomized into 4 groups for a 4 week period of time; placebo, 2.5 mg, 5 mg, or 10 mg three times daily. The BE/SDS subgroup demonstrated a 27 +/- 8% (22 mmHg) increase in standing systolic blood pressure for the 10 mg dose. Diabetics achieved a significant increase at 5 mg. Similar increases were observed for the entire group on the 10 mg dose (p
A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. [2019]To determine the best therapeutic strategy for the use of midodrine in patients with neurogenic orthostatic hypotension (NOH).