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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.
Patients with autonomic failure cannot regulate blood pressure properly. Upon standing, their blood pressure drops (i.e. orthostatic hypotension) and may cause symptoms such as lightheadedness, dizziness, changes in vision, weakness, fatigue, trouble concentrating, and shoulder and neck pain. Orthostatic hypotension can be severe and disabling; it can lead to frequent loss of consciousness and falls. These symptoms can make it difficult to perform activities of daily living resulting in significant impairment of the patient's quality of life. Thus, the assessment of orthostatic symptoms using validated questionnaires has been one of the main tools to determine the efficacy of treatment approaches for orthostatic hypotension. However, its usefulness may be limited by several factors including difficulty in the categorization of symptoms and rating of their severity, particularly in patients with some degree of cognitive impairment; the confounding effect of factors not related to orthostatic hypotension on patient's symptoms; difficulty in performing an accurate comparison of the severity of symptoms before and after treatment or between treatments; underestimating symptom burden by not reporting symptoms that are not included in the validated questionnaires or by problems in the patient recall.
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. The main hypothesis is that the quantification of upright time (standing and walking) with an activity monitor would be useful in the assessment of the severity of neurogenic orthostatic hypotension and the efficacy of the treatment for this condition and whether it would be superior to the assessment of symptoms using validated questionnaires.
Patients with autonomic failure and neurogenic orthostatic hypotension on treatment with either midodrine or atomoxetine will be eligible for this study. The study will take place at the participant's home with the assistance of his or her caregiver and frequent oversight from the investigative team. Participants will be studied for two separate weeks, one week with placebo and one week with their regular treatment (midodrine or atomoxetine at their usual doses), with one week in between for washout (the period of using participants' usual medication without any study measurement performed). The order of the study weeks with placebo or regular treatment will be randomized and the study medications will be blinded. On each study week, participants will be asked to wear an activity monitor (Activpal) on one of their thighs to measure the amount of time they spend in the upright posture (walking and standing), number of steps, activity and other characteristics related to the quantity and quality of walking and standing. Participants will be guided to write down the times of their daily activities, such as waking, sleeping, eating, and taking medication. At the end of each study week, the participants will be guided to fill out some questionnaires, and to take blood pressure measurements while lying down, sitting, and standing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| placebo | Experimental | Placebo pill will be taken for 7 days at the same frequency as their regular treatment with either midodrine or atomoxetine. |
|
| Standard treatment | Active Comparator | Either midodrine or atomoxetine at their regular dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Accelerometer | Device | A uniaxial accelerometer-based activity monitor (ActivpalTM) will be worn by participants on one of the thighs during the 7 days of the placebo and treatment periods. |
| Measure | Description | Time Frame |
|---|---|---|
| Total standing time measured by an accelerometer | The percentage of total standing time during the treatment or placebo period will be measured by an accelerometer (Activpal) placed on one of the patient's thighs. The accelerometer quantifies the length of time spent in the upright and seated or supine positions. | 7 days of the treatment or placebo period |
| Orthostatic symptoms | Orthostatic symptoms measured by the Orthostatic Hypotension Questionnaire (OHQ). The questionnaire is divided into two parts: Part I, Symptom Assessment (OHSA), consisted of six questions, each rating the intensity of one characteristic symptom of OH: 1) Dizziness, lightheadedness, feeling faint, or feeling like you might blackout; 2) Blurring, seeing spots or tunnel vision; 3) Generalized weakness; 4) Fatigue; 5) Trouble concentrating; 6) Head/neck discomfort; and Part II, Daily Activity Scale (OHDAS), consisted of four questions that assessed the impact of neurogenic OH symptoms on daily activities. The recall period is ''over the past week''. The items are scored on an 11-point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference, and the option of selecting ''cannot be done for other reasons''. The composite OHQ score is calculated by averaging the OHSAS and the OHDAS. | 7 days of treatment or placebo period |
| Measure | Description | Time Frame |
|---|---|---|
| Total number of steps measured by an accelerometer | Number of steps during the treatment or placebo period will be measured by an accelerometer (Activpal) placed on one of the patient's thighs | 7 days of treatment or placebo period |
| Total walking time measured by an accelerometer |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bonnie K Black, RN | Contact | 615-343-6862 | autonomics@vumc.org |
| Name | Affiliation | Role |
|---|---|---|
| Italo Biaggioni, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Autonomic Dysfunction Center/ Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37232 | United States |
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placebo-controlled, double-blind, randomized crossover
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Participants and outcome assessor will be blinded to the study medications
|
| placebo pill | Drug | Placebo pill will be taken for 7 days at the same frequency as their regular treatment with either midodrine or atomoxetine. |
|
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| Midodrine or atomoxetine pill | Drug | Either midodrine or atomoxetine at their regular dose. |
|
Total walking time during the treatment or placebo period will be measured by an accelerometer (Activpal) placed on one of the patient's thighs. The accelerometer quantifies the length of time spent walking, standing still, and sitting or lying down. |
| 7 days of treatment or placebo period |
| ID | Term |
|---|---|
| D007022 | Hypotension |
| D054970 | Pure Autonomic Failure |
| D019578 | Multiple System Atrophy |
| D020734 | Parkinsonian Disorders |
| D007024 | Hypotension, Orthostatic |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D054971 | Orthostatic Intolerance |
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| ID | Term |
|---|---|
| D000073893 | Sugars |
| D008879 | Midodrine |
| D000069445 | Atomoxetine Hydrochloride |
| ID | Term |
|---|---|
| D002241 | Carbohydrates |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D011437 | Propylamines |
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