Back to resultsStudy to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension
Primary Purpose
Hypotension, Orthostatic
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Midodrine hydrochloride
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypotension, Orthostatic
Eligibility Criteria
Inclusion Criteria:
- The male or female subjects must be 18 years of age or older and ambulatory. (Subjects must not require assistance with a walker or wheelchair to perform regular daily activities at all times.)
- Women of childbearing potential must have a negative serum beta HCG pregnancy test at screening and baseline.
- The subject has been diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathy (i.e. neurogenic orthostatic hypotension).
- The subject manifests one of the following symptoms while standing or has a history of one of the following when not treated for orthostatic hypotension: dizziness, lightheadedness, feeling faint or feeling like they may black out.
- The subject is willing and able to undergo the procedures required by this protocol including morning office visits, assessment completion, protocol compliance and participation in the wash-out period.
- The subject has signed an Institutional-Review-Board approved written informed consent form prior to any study procedures taking place.
Exclusion Criteria:
- The subject is a pregnant or lactating female.
- The subject has pre-existing sustained supine hypertension greater than 180 mm Hg systolic and 110 mm Hg diastolic.
- The subject is taking medications such as vasodilators, pressors, diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers, combined alpha and beta-blockers, MAOI's, herbals or specific mixed effect medications.
- The Principal Investigator deems any laboratory test abnormality clinical significant.
- The subject has a diagnosis of any of the following disorders at the time of screening: pheochromocytoma; cardiac conditions including: congestive heart failure within the previous 6 months, myocardial infarction within the previous 6 months, symptomatic coronary artery disease, history of ventricular tachycardia, or uncontrolled cardiac arrhythmias; thyrotoxicosis; uncontrolled diabetes mellitus (uncontrolled defined as a HgbA1c greater than or equal to 10%); history of cerebrovascular accident, transient ischemic attack (TIA) or symptomatic carotid artery stenosis within the previous 6 months; history of coagulopathies; pulmonary hypertension; severe psychiatric disorders; renal failure (Creatinine equal to or greater than 2 times the upper limit of normal)
- The subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of the tests and/or measurements administered in this trial, or that might increase the risk to the subject.
Sites / Locations
- Fort Wayne Neurological Center
- Beth Israel Deaconess Medical Center
- University of Michigan
- Minnesota VA Medical Center
- Forest Park Neurophysiology
- Mount Sinai Medical Center
- Raleigh Neurology Associates
- University Hospitals of Cleveland
- Absher Neurology, PA
- Vanderbilt University
- Diabetes and Glandular Disease research Associates, PA
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Outcomes
Primary Outcome Measures
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 1 but the summary data are presented as least squares mean (standard error).
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. The Koch procedure is a 3-step process to analyze results while utilizing the available information on magnitude of differences.
Secondary Outcome Measures
Time to Onset of Near-syncopal Symptoms in The Per-protocol Population
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 4 but the summary data are presented as least squares mean (standard error).
Time to Near-syncopal Symptoms at Treatment Visit 1
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Duration of The Effect of Treatment at 3 Hours Post-dose
Duration of effect was defined as the difference in time to onset of near-syncopal symptoms between the first and second tilt table test, conducted at 1 hour and 3 hours post-dose, respectively, at Treatment Visit 2 (time to onset at 3 hours minus time at 1 hour). The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)
The OHSA measures the severity of six symptoms/symptom complexes associated with orthostatic hypotension. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". The OHSA total score is the sum of six subscales, ranging from 0 (no symptoms) to 60 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Scores for 6 Items of The OHSA
The OHSA measures the severity of six symptoms/symptom complexes associated with OH: dizziness, lightheadedness, and feeling faint; problems with vision; weakness; fatigue; trouble concentrating; and head/neck discomfort. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". Scores for each subscale range from 0 (no symptoms) to 10 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, and feeling faint.
Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The clinician completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The patient completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Final Blood Pressure During Tilt Table Testing
Blood pressure was recorded just before tilt table testing and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
Heart rate was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
For hematology, blood samples (5.0mL) were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: hemoglobin, hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count - total and differential (WBC), and platelet count. A shift in reference to normal was either lower or higher at discharge.
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
For biochemistry, blood samples (10.0mL) were taken at screening, admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: sodium, potassium, calcium, blood urea nitrogen (BUN)/Urea, creatinine, albumin, total protein and albumin/globulin (A/G) ratio, globulin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, glucose, chloride, and creatine kinase. A shift in reference to normal was either lower or higher at discharge.
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
For urinalysis, samples were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination): glucose, blood, protein, pH, specific gravity, leukocyte esterase, and microscopic examination. A shift in reference to normal was higher at discharge.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00555880
Brief Title
Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension
Official Title
A Multi-Center, Double-Blind, Randomized, Placebo-controlled, Crossover Study to Assess the Clinical Benefit of Midodrine Hydrochloride in Subjects With Moderate to Severe Neurogenic Orthostatic Hypotension
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
September 8, 2004 (Actual)
Primary Completion Date
March 21, 2005 (Actual)
Study Completion Date
March 21, 2005 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
5. Study Description
Brief Summary
The purpose of this clinical study is to evaluate the clinical effect of midodrine hydrochloride (ProAmatine®) compared to placebo in patients with orthostatic hypotension by measuring the time to onset of near syncopal symptoms and assessing several cardiovascular measurements, such as heart rate, blood pressure, and ECG, using the tilt table test.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypotension, Orthostatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Midodrine hydrochloride
Other Intervention Name(s)
ProAmatine
Intervention Description
one dose, 10-30mg, given orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
Description
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 hour post-dose
Title
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2
Description
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 1 but the summary data are presented as least squares mean (standard error).
Time Frame
1 hour post-dose
Title
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure
Description
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. The Koch procedure is a 3-step process to analyze results while utilizing the available information on magnitude of differences.
Time Frame
1 hour post-dose
Secondary Outcome Measure Information:
Title
Time to Onset of Near-syncopal Symptoms in The Per-protocol Population
Description
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 hour post-dose
Title
Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2
Description
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 4 but the summary data are presented as least squares mean (standard error).
Time Frame
1 hour post-dose
Title
Time to Near-syncopal Symptoms at Treatment Visit 1
Description
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 hour post-dose
Title
Duration of The Effect of Treatment at 3 Hours Post-dose
Description
Duration of effect was defined as the difference in time to onset of near-syncopal symptoms between the first and second tilt table test, conducted at 1 hour and 3 hours post-dose, respectively, at Treatment Visit 2 (time to onset at 3 hours minus time at 1 hour). The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 and 3 hours post-dose
Title
Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)
Description
The OHSA measures the severity of six symptoms/symptom complexes associated with orthostatic hypotension. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". The OHSA total score is the sum of six subscales, ranging from 0 (no symptoms) to 60 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
Approximately 1 hour post-dose
Title
Scores for 6 Items of The OHSA
Description
The OHSA measures the severity of six symptoms/symptom complexes associated with OH: dizziness, lightheadedness, and feeling faint; problems with vision; weakness; fatigue; trouble concentrating; and head/neck discomfort. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". Scores for each subscale range from 0 (no symptoms) to 10 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, and feeling faint.
Time Frame
Approximately 1 hour post-dose
Title
Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
Description
The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The clinician completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 and 3 hours post-dose
Title
Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
Description
The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The patient completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 and 3 hours post-dose
Title
Final Blood Pressure During Tilt Table Testing
Description
Blood pressure was recorded just before tilt table testing and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 hour post-dose
Title
Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
Description
Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 and 3 hours post-dose
Title
Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
Description
Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 and 3 hours post-dose
Title
Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
Description
Heart rate was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time Frame
1 and 3 hours post-dose
Title
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
Description
For hematology, blood samples (5.0mL) were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: hemoglobin, hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count - total and differential (WBC), and platelet count. A shift in reference to normal was either lower or higher at discharge.
Time Frame
Baseline to discharge
Title
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Description
For biochemistry, blood samples (10.0mL) were taken at screening, admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: sodium, potassium, calcium, blood urea nitrogen (BUN)/Urea, creatinine, albumin, total protein and albumin/globulin (A/G) ratio, globulin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, glucose, chloride, and creatine kinase. A shift in reference to normal was either lower or higher at discharge.
Time Frame
Baseline to discharge
Title
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Description
For urinalysis, samples were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination): glucose, blood, protein, pH, specific gravity, leukocyte esterase, and microscopic examination. A shift in reference to normal was higher at discharge.
Time Frame
Baseline to discharge
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The male or female subjects must be 18 years of age or older and ambulatory. (Subjects must not require assistance with a walker or wheelchair to perform regular daily activities at all times.)
Women of childbearing potential must have a negative serum beta HCG pregnancy test at screening and baseline.
The subject has been diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathy (i.e. neurogenic orthostatic hypotension).
The subject manifests one of the following symptoms while standing or has a history of one of the following when not treated for orthostatic hypotension: dizziness, lightheadedness, feeling faint or feeling like they may black out.
The subject is willing and able to undergo the procedures required by this protocol including morning office visits, assessment completion, protocol compliance and participation in the wash-out period.
The subject has signed an Institutional-Review-Board approved written informed consent form prior to any study procedures taking place.
Exclusion Criteria:
The subject is a pregnant or lactating female.
The subject has pre-existing sustained supine hypertension greater than 180 mm Hg systolic and 110 mm Hg diastolic.
The subject is taking medications such as vasodilators, pressors, diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers, combined alpha and beta-blockers, MAOI's, herbals or specific mixed effect medications.
The Principal Investigator deems any laboratory test abnormality clinical significant.
The subject has a diagnosis of any of the following disorders at the time of screening: pheochromocytoma; cardiac conditions including: congestive heart failure within the previous 6 months, myocardial infarction within the previous 6 months, symptomatic coronary artery disease, history of ventricular tachycardia, or uncontrolled cardiac arrhythmias; thyrotoxicosis; uncontrolled diabetes mellitus (uncontrolled defined as a HgbA1c greater than or equal to 10%); history of cerebrovascular accident, transient ischemic attack (TIA) or symptomatic carotid artery stenosis within the previous 6 months; history of coagulopathies; pulmonary hypertension; severe psychiatric disorders; renal failure (Creatinine equal to or greater than 2 times the upper limit of normal)
The subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of the tests and/or measurements administered in this trial, or that might increase the risk to the subject.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Fort Wayne Neurological Center
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46805
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Minnesota VA Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417
Country
United States
Facility Name
Forest Park Neurophysiology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63139
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Raleigh Neurology Associates
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Absher Neurology, PA
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Diabetes and Glandular Disease research Associates, PA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension
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