Clinical trial NCT00046475: A Study for 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 Patients With Neurogenic Orthostatic Hypotension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypotension, Orthostatic
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2002-10-02
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease.

The purpose of this clinical study is to further assess the clinical benefit of midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down and standing positions will be measured at each visit.


Eligibility criteria: Inclusion Criteria:

* The male or female patient must be 18 years of age or older and ambulatory.
* Female patients must be: without menses for at least 12 months prior to screening; surgically sterilized (bilateral tubal ligation or hysterectomy); or practicing adequate means of birth control. Adequate means of birth control is defined as the use of prescribed birth control pills, IUD, or hormonal injections from at least one month prior to screening. Double-barrier methods and abstinence are also acceptable forms of birth control.
* The patient has been diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension).
* The patient manifests at least 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 patient 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 patient signs an Institutional-Review-Board approved written Informed Consent form prior to any study procedures taking place.

Exclusion Criteria:

* The patient is pregnant or lactating female.
* The patient has pre-existing sustained supine hypertension greater than 180 systolic and 110 diastolic mmHg.
* The patient 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 clinically significant.
* The patient 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 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 patient 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 patient.

Primary outcomes:
measure: Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale
timeFrame: End of 2-week treatment period
measure: Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites
timeFrame: End of 2-week treatment period
measure: Post-treatment OHSA Item 1 Score of United States (US) Participants With Mild/Moderate Disease According to The Clinical Global Impressions-Severity (CGI-S) Scale
timeFrame: End of 2-week treatment period
measure: Post-treatment OHSA Item 1 Score of US Participants With Marked/Severe Disease According to The CGI-S Scale
timeFrame: End of 2-week treatment period
Secondary outcomes:
measure: Change From Baseline in The OHSA Items 2 Through 6 Scores
timeFrame: From the time of titration until the end of treatment
measure: Change From Baseline in The OHSA Composite Symptom Score
timeFrame: From the time of titration until the end of treatment
measure: Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores
timeFrame: From the time of titration until the end of treatment
measure: Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score
timeFrame: From the time of titration until the end of treatment
measure: Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale
timeFrame: From the time of titration until the end of treatment
measure: Percent of Participants Scored as Improved on The Patient Version of The CGI-I Scale
timeFrame: From the time of titration until the end of treatment
measure: Change From Baseline in Standing Blood Pressure (BP)
timeFrame: From the time of titration until the end of treatment
measure: Change From Baseline in Supine BP
timeFrame: From the time of titration until the end of treatment
measure: Change From Baseline in Short Form-36 (SF-36) Version 2 Health Survey Questionnaire Scores
timeFrame: From the time of titration until the end of treatment
measure: Test Reliability of the Intent-to-Treat (ITT) Population
timeFrame: From the time of titration until the end of treatment
measure: Responsiveness of the Intent-to-Treat (ITT) Population
timeFrame: From the time of titration until the end of treatment
measure: Convergent Validity of the Intent-to-Treat (ITT) Population
timeFrame: From the time of titration until the end of treatment
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: North Alabama Neuroscience Research
state: Alabama
city: Miramar
country: United States
facility: Dr. Harry Pepe & Associates, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates, Inc.
state: Florida
city: Chicago
country: United States
facility: Economou & Associates, LTD
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Pain and Neurological Institute
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: NY Presbyterian Hospital
state: New York
city: Toledo
country: United States
facility: Medical College of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research, LLC
state: Oklahoma
city: Greensburg
country: United States
facility: Westmoreland Neurology Associates Inc.
state: Pennsylvania
city: Upland
country: United States
facility: Neurological Associates of Delaware Valley
state: Pennsylvania
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Associates, PA
state: Texas
city: Norfolk
country: United States
facility: Monarch Medical Research
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: