Treatment of Orthostatic Intolerance in Patients With Parkinson's Disease Using Midodrine

This study will evaluate whether treatment with the α1-agonist, midodrine, reduces subjective orthostatic lightheadedness as measured by the Non-Motor Symptoms Scale for Parkinson's Disease (NMSS) questionnaire, in patients with (positive control group, OH) or without documented orthostatic hypotension(orthostatic intolerance, OI). It will also demonstrate the effect of treatment with an α1-agonist, midodrine, on beat-to-beat blood pressure and heart rate response during Valsalva maneuver (measured by Continuous Non-invasive Arterial Pressure, CNAP) in patients with OI or OH and evaluate the relationship to symptom improvement.

Study Overview

• Status: Unknown
• Conditions: Parkinson's Disease; Orthostatic Intolerance
• Intervention / Treatment: Drug: Midodrine

Detailed Description

This will be a cross-over study where participants with OI will be randomized to initially receive midodrine or placebo then crossed over to the opposite treatment after three weeks (2 weeks on midodrine or placebo plus one week wash out period). The control group will consist of participants with OH and PD being treated with midodrine. Basic demographic data including will be collected from the medical record of each participant after consent. At each study visit, each participant will undergo traditional measurement of blood pressure and heart rate as well as measurement of beat-to-beat blood pressure and heart rate using CNAP™ during valsalva maneuver and in response to standing for 5 minutes after sitting. Symptoms of orthostatic intolerance will be measured during the study visit using Domain 1 of the Non-Motor Symptoms Scale for Parkinson's Disease (NMSS). At the initial study visit, participants will also be administered first dose of midodrine or placebo. Supine sitting, and standing systolic and diastolic blood pressure and pulse rates will be measured immediately before and 1 hour after the administration of drug or placebo. This blood pressure monitoring process will take place at each of the four study visits.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: James Morley, MD/Ph.D.; Phone Number: 215-823-5934
• Study Contact Backup: Name: Stephanie Wood; Phone Number: 215-823-5934

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • PVAMC
      • Contact: James Morley, MD/Ph.D.; Phone Number: 215-823-5934

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with a diagnosis of idiopathic Parkinson's Disease
2. Those patients with measured orthostatic hypotension will be included in the positive control group
3. Those patients without measurable orthostatic hypotension who have symptoms of lightheadedness on standing will be included in the study group

Exclusion Criteria:

1. Diagnosis of degenerative parkinsonian syndromes other than idiopathic Parkinson's Disease
2. Inability to stand independently and remain standing for 5 minutes
3. Cognitive impairment that is significant enough to affect the ability of the patient to provide informed consent or to reliably report orthostatic symptoms
4. Patients with a pacemaker will also be excluded because the study is measuring heart rate responses which could potentially be altered by a pacemaker
5. Because this study will be using a drug that can affect blood pressure, those patients with a standing BP of > 139/90 and heart rate <60 will be excluded
6. Because this study will be using a drug that can affect supine hypertension, those patients with a supine BP of >139/90 and heart rate <60 will be excluded
7. Current treatment with other drugs for orthostatic hypotension such as fludrocortisone
8. Patients on phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine, dihydroergotamine
9. Patients with acute or chronic renal failure (GFR <60)
10. Patients with a history of pheochromocytoma, urinary retention, severe cardiac disease, history of congestive heart failure, diabetes, narrow-angle glaucoma, arrhythmias, bradycardia, severe hyperthyroidism, severe difficult urination (due to urinary retention or enlarged prostate)
11. Pregnant or breast-feeding women.
12. Women of childbearing potential with no effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy.
13. Women of childbearing potential must have a confirmed negative pregnancy test at screening and randomization visits. They must use an effective contraceptive method throughout the study, and agree to repeat urine pregnancy test at designated visits. The applied methods of contraception have to meet the criteria for a highly effective method of birth control (condoms, FDA approved oral contraceptives, patches, injections, rings, IUD).
14. Patients with known drug allergy or hypersensitive to midodrine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo given three times a day for 2 weeks
Active Comparator: Midodrine; Midodrine 2.5 mg given three times a day for one week followed by 5 mg given three times a day for one week	Drug: Midodrine; Crossover intervention comparing midodrine to placebo for subjects with orthostatic intolerance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NMSS Domain I (improvement in symptoms of lightheadedness when standing)	improvement in symptoms of lightheadedness when standing	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Valsalva response (Beat-to-beat blood pressure and heart rate variation during Valsalva maneuver)	Beat-to-beat blood pressure and heart rate variation during Valsalva maneuver	7 weeks

Collaborators and Investigators

• Sponsor: Corporal Michael J. Crescenz VA Medical Center
• Investigators: Principal Investigator: James Morley, DOMD/Ph.D., PVAMC

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 17, 2015
• First Posted (Estimate): February 18, 2015

Study Record Updates

• Last Update Posted (Estimate): August 26, 2015
• Last Update Submitted That Met QC Criteria: August 25, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Parkinson Disease; Orthostatic Intolerance; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: 01482