Clinical trial NCT00555880: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypotension, Orthostatic
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-11-09
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
timeFrame: 1 hour post-dose
measure: Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2
timeFrame: 1 hour post-dose
measure: Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure
timeFrame: 1 hour post-dose
Secondary outcomes:
measure: Time to Onset of Near-syncopal Symptoms in The Per-protocol Population
timeFrame: 1 hour post-dose
measure: Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2
timeFrame: 1 hour post-dose
measure: Time to Near-syncopal Symptoms at Treatment Visit 1
timeFrame: 1 hour post-dose
measure: Duration of The Effect of Treatment at 3 Hours Post-dose
timeFrame: 1 and 3 hours post-dose
measure: Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)
timeFrame: Approximately 1 hour post-dose
measure: Scores for 6 Items of The OHSA
timeFrame: Approximately 1 hour post-dose
measure: Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
timeFrame: 1 and 3 hours post-dose
measure: Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
timeFrame: 1 and 3 hours post-dose
measure: Final Blood Pressure During Tilt Table Testing
timeFrame: 1 hour post-dose
measure: 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
timeFrame: 1 and 3 hours post-dose
measure: 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
timeFrame: 1 and 3 hours post-dose
measure: Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
timeFrame: 1 and 3 hours post-dose
measure: Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
timeFrame: Baseline to discharge
measure: Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
timeFrame: Baseline to discharge
measure: Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
timeFrame: Baseline to discharge
Other outcomes:
Locations:
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota VA Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Forest Park Neurophysiology
state: Missouri
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Greenville
country: United States
facility: Absher Neurology, PA
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease research Associates, PA
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: