Clinical Trial: A Study for Patients With Neurogenic Orthostatic Hypotension

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Hy

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.


Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

  • Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale [ Time Frame: End of 2-week treatment period ]
    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.
  • Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites [ Time Frame: End of 2-week treatment period ]
    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.
  • 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 [ Time Frame: End of 2-week treatment period ]
    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

    Original Primary Outcome:

    Current Secondary Outcome:

    • Change From Baseline in The OHSA Items 2 Through 6 Scores [ Time Frame: From the time of titration until the end of treatment ]
      Items 2 through 6 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 the following symptoms whenever he or she was standing and that improved when he or she sat down or laid down: Item 2 addresses problems with vision (blurring, seeing spots, tunnel vision, etc); Item 3, weakness; Item 4, fatigue; Item 5, trouble concentrating; and Item 6, head or neck discomfort. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved.
    • Change From Baseline in The OHSA Composite Symptom Score [ Time Frame: From the time of titration until the end of treatment ]
      The OHSA composite symptom score was calculated by taking the average of the ratings for the symptoms present at Baseline. Participants were asked to rate symptoms by using a 0-10 scale (0 meaning not bothered and 10 meaning the worst). For subsequent visits, only those symptoms present at Baseline were scored. In this manner, a score was produced that represents the severity (and subsequent change in severity) of the patient's neurogenic OH symptoms, regardless of how many symptoms are presented at Baseline. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved.
    • Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores [ Time Frame: From the time of titration until the end of treatment ]
      The OHDAS had 4 items that asked the patient to give a graduated score from 0 (no limitation due to OH) to 10 (complete limitation due to OH). Item 1 addressed activities that required standing for a short time; Item 2, activities that required standing for a long time; Item 3, activities that required walking for a short time; and Item 4, activities that required walking for a long time. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved.
    • Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score [ Time Frame: From the time of titration until the end of treatment ]
      The OHDAS global daily activity score was calculated as the average of all daily activity item scores. The OHDAS had 4 items that asked the patient to give a graduated score from 0 (no limitation due to OH) to 10 (complete limitation due to OH) to activities that required standing for a short time, standing for a long time, walking for a short time, walking for a long time. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved.
    • Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale [ Time Frame: From the time of titration until the end of treatment ]
      The CGI-I is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Clinical Global Impressions ratings are completed with respect to neurogenic OH symptoms. A value of 0 was used if the investigator or patient assessment was not performed. The improved category is made up of patients who were evaluated as very much improved, much improved, or slightly improved for the classification of "Overall Improvement." The CGI-I was completed at Visit 5 (Period 2) and Visit 6 (study completion).
    • Percent of Participants Scored as Improved on The Patient Version of The CGI-I Scale [ Time Frame: From the time of titration until the end of treatment ]
      The CGI-I is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Clinical Global Impressions ratings are completed with respect to neurogenic OH symptoms. A value of 0 was used if the investigator or patient assessment was not performed. The improved category is made up of patients who were evaluated as very much improved, much improved, or slightly improved for the classification of "Overall Improvement." The CGI-I was completed at Visit 5 (Period 2) and Visit 6 (study completion).
    • Change From Baseline in Standing Blood Pressure (BP) [ Time Frame: From the time of titration until the end of treatment ]
      Standing BP was measured at Visit 5 (Period 2) and Visit 6 (study completion) and compared to measurements taken at Visit 3A (titration). Standing BP was measured 3 minutes after the patient rose from the supine position or as soon as the patient indicated they needed to sit down. If the patient indicated he or she needed to sit down, the BP measurement was taken while in the standing position, before the patient sat down.
    • Change From Baseline in Supine BP [ Time Frame: From the time of titration until the end of treatment ]
      Supine BP was measured at Visit 5 (Period

      Original Secondary Outcome:

      Information By: Shire

      Dates:
      Date Received: September 30, 2002
      Date Started: January 2002
      Date Completion:
      Last Updated: May 13, 2015
      Last Verified: November 2007