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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

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.

Lead Sponsor: Shire Pharmaceutical Development

North Alabama Neuroscience Research

Huntsville Alabama 35801 United States

Dr. Harry Pepe & Associates, Inc.

Miramar Florida 33023 United States

Suncoast Neuroscience Associates, Inc.

St. Petersburg Florida  United States

Economou & Associates, LTD

Chicago Illinois 60612 United States

Johns Hopkins Hospital

Baltimore Maryland  United States

Michigan Pain and Neurological Institute

Ann Arbor Michigan  United States

Dartmouth Hitchcock Medical Center

Lebanon New Hampshire 03756 United States

NY Presbyterian Hospital

New York New York 10032 United States

Medical College of Ohio

Toledo Ohio 43614 United States

COR Clinical Research, LLC

Oklahoma City Oklahoma 73103 United States

Neurological Associates of Delaware Valley

Upland Pennsylvania 19013 United States

Westmoreland Neurology Associates Inc.

Greensburg Pennsylvania 15601 United States

Diabetes & Glandular Disease Research Associates, PA

San Antonio Texas  United States

Monarch Medical Research

Norfolk Virginia 23502 United States

West Virginia University

Morgantown West Virginia 26506 United States

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00046475

Study ID Number: 20,762-401

ClinicalTrials.gov Identifier: NCT00046475

Health Authority: United States: Food and Drug Administration

The National Dysautonomia Research Foundation

Clinical Trials Resource Site