A Study for Patients With Neurogenic Orthostatic Hypotension

NCT00046475 | Completed Phase 4 Results

• 1 other identifier: 20,762-401
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 15

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.

Conditions

Hypotension, Orthostatic

Outcome Measures

Primary Outcomes (4)

• Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale

  Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease.

  End of 2-week treatment period

• Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites

  Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease.

  End of 2-week treatment period

• 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

  Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. The results are reported by degree of severity according to the CGI-S scale, which uses 4 categories to describe disease severity: Mild, Moderate, Marked, and Severe. The Item 1 scores reported are grouped for participants with Mild or Moderate disease severity. Higher scores indicate more severe disease.

  End of 2-week treatment period

• Post-treatment OHSA Item 1 Score of US Participants With Marked/Severe Disease According to The CGI-S Scale

  Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. The results are reported by degree of severity according to the CGI-S scale, which uses 4 categories to describe disease severity: Mild, Moderate, Marked, and Severe. The Item 1 scores reported are grouped for participants with Marked or Severe disease severity. Higher scores indicate more severe disease.

  End of 2-week treatment period

Secondary Outcomes (12)

• Change From Baseline in The OHSA Items 2 Through 6 Scores

  From the time of titration until the end of treatment

• Change From Baseline in The OHSA Composite Symptom Score

  From the time of titration until the end of treatment

• Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores

  From the time of titration until the end of treatment

• Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score

  From the time of titration until the end of treatment

• Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale

  From the time of titration until the end of treatment

Interventions

Midodrine Hydrochloride DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (15)

North Alabama Neuroscience Research

Huntsville, Alabama, 35801, United States

Location

Dr. Harry Pepe & Associates, Inc.

Miramar, Florida, 33023, United States

Location

Suncoast Neuroscience Associates, Inc.

St. Petersburg, Florida, United States

Location

Economou & Associates, LTD

Chicago, Illinois, 60612, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, United States

Location

Michigan Pain and Neurological Institute

Ann Arbor, Michigan, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

NY Presbyterian Hospital

New York, New York, 10032, United States

Location

Medical College of Ohio

Toledo, Ohio, 43614, United States

Location

COR Clinical Research, LLC

Oklahoma City, Oklahoma, 73103, United States

Location

Westmoreland Neurology Associates Inc.

Greensburg, Pennsylvania, 15601, United States

Location

Neurological Associates of Delaware Valley

Upland, Pennsylvania, 19013, United States

Location

Diabetes & Glandular Disease Research Associates, PA

San Antonio, Texas, United States

Location

Monarch Medical Research

Norfolk, Virginia, 23502, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Related Links

• The National Dysautonomia Research Foundation
• Clinical Trials Resource Site

MeSH Terms

Conditions

Hypotension, Orthostatic

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2002
• First Posted: October 2, 2002
• Study Start: December 1, 1997
• Primary Completion: November 24, 1999
• Study Completion: November 24, 1999
• Last Updated: June 11, 2021
• Results First Posted: May 12, 2015

Record last verified: 2021-06

Locations

US (15)