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.
Male and female subjects, age 40-80 years.
Possible or probable Multiple Systems Atrophy, Pure Autonomic Failure, or Parkinson's disease with neurogenic orthostatic hypotension.
Neurogenic orthostatic hypotension defined as a ≥ 30 mmHg decrease in systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
Patients on treatment for neurogenic orthostatic hypotension with either midodrine or atomoxetine, who have experienced some improvement in their orthostatic symptoms, but still remain symptomatic (Orthostatic hypotension symptom assessment [OHSA] score of 1 to 5 while on medication).
Bedridden, physically disabled, or unable to walk.
Patients with Orthostatic hypotension symptom assessment (OHSA) score ≥ 6, or orthostatic systolic blood pressure drop ≥ 30 mmHg on their regular treatment.
Patients taking more than one medication for the treatment of neurogenic orthostatic hypotension (concomitant use of pyridostigmine or fludrocortisone are accepted).
Pregnancy
Crossover
Accelerometer
DeviceA 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.
placebo pill
DrugPlacebo pill will be taken for 7 days at the same frequency as their regular treatment with either midodrine or atomoxetine.
Midodrine or atomoxetine pill
DrugEither midodrine or atomoxetine at their regular dose.
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.
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.
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
Total walking time measured by an accelerometer
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.
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