A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride

NCT00426842 | Completed Phase 2 Results

• 2 other identifiers: 00893VA Project #5481-06-051
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

With upright postures, there is an immediate redistribution of blood to the dependent circulation; venous return and central venous filling pressure are reduced, resulting in diminution of cardiac output and blood pressure. These hemodynamic alterations stimulate the baroreceptor reflex, which is mediated via the central nervous system to increase peripheral sympathetic vasomotor tone, restoring blood pressure and cardiac output within seconds-to-minutes of the assumption of the upright position. Following SCI, individuals often experience the inability to adjust to postural changes due to disruption of central command of the baroreceptor reflex and reduction in efferent sympathetic neural pathways; consequently, orthostatic hypotension (OH) and symptoms of cerebral hypo-perfusion may ensue. OH is a well-documented phenomenon, which is characterized by a fall in systolic blood pressure of \>20 mmHg or diastolic BP of \> 10 mmHg within 3 minutes of assumption of an upright posture. As a consequence of OH, many individuals experience symptoms of cerebral hypo-perfusion which include lightheadedness, dizziness, blurry vision, fatigue, nausea, ringing in the ears, cognitive impairment and heart palpitations. Although several investigators have reported increased prevalence of OH during the acute phase of spinal cord injury (SCI), individuals with chronic injury also experience significant falls in blood pressure with seated upright postures. This investigation will examine the effects of an alpha-agonist, midodrine hydrochloride, during head-up tilt on systemic blood pressure, cerebral blood flow and cerebral oxygenation compared to placebo administration in persons with chronic SCI who demonstrate significant orthostatic hypotension during a 24-hour observation study. This is the first study to determine the dose response and efficacy of midodrine to improve orthostatic blood pressure and cerebral blood flow and oxygenation in the SCI population.

Conditions

Orthostatic Hypotension; Spinal Cord Injury

Keywords

Blood pressure; Orthostatic hypotension; Spinal Cord Injury; Sympathetic vascular control; Midodrine

Outcome Measures

Primary Outcomes (1)

• Systolic Blood Pressure

  brachial artery systolic blood pressure (mmHg)

  The difference between the average supine systolic blood pressure and the average systolic blood pressure at 45 degree head-up tilt position.

Study Arms (1)

Arm 1

EXPERIMENTAL

Blood pressure response during HUT following administration of Midodrine Hydrochloride compared with no drug.

Drug: Midodrine Hydrochloride

Interventions

Midodrine Hydrochloride DRUG

Alpha1-agonist, exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure.

Arm 1

Eligibility Criteria

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

You may qualify if:

• This study will be performed on subjects 18 to 65 years old, with chronic SCI (\> 1 year), who are neurologically stable and have demonstrated significant hypotension (total time \[proportion 50%\] spent with hypotension \[systolic BP below 110 mmHg for males and 100 mmHg for females\] during a 24-hour observation.

You may not qualify if:

• hypertension
• diabetes
• vascular disease
• cardiac disease
• cardiovascular medication
• pregnancy

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead

Study Sites (1)

VA Medical Center, Bronx

The Bronx, New York, 10468, United States

Location

Related Publications (2)

• Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA. Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil. 2010 Sep;91(9):1429-35. doi: 10.1016/j.apmr.2010.06.017.

  PMID: 20801263 RESULT

• Wecht JM, Radulovic M, Rosado-Rivera D, Zhang RL, LaFountaine MF, Bauman WA. Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia. Arch Phys Med Rehabil. 2011 Nov;92(11):1789-95. doi: 10.1016/j.apmr.2011.03.022. Epub 2011 Jul 16.

  PMID: 21762873 RESULT

MeSH Terms

Conditions

Hypotension, Orthostatic; Spinal Cord Injuries

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Limitations and Caveats

A matching placebo tablet was not used and the order of testing was not randomized. The total number of subjects recruited was relatively small and extrapolation to a broader group of individuals with chronic SCI may not be appropriate.

Results Point of Contact

• Title: Dr. Jill M. Wecht
• Organization: James J Peters VAMC

jm.wecht@va.gov

718-584-9000

Study Officials

• Jill Wecht, EdD

  VA Medical Center, Bronx

  PRINCIPAL INVESTIGATOR

• William Bauman, MD

  VA Medical Center, Bronx

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Scientist

Study Record Dates

• First Submitted: January 24, 2007
• First Posted: January 25, 2007
• Study Start: January 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: October 10, 2016
• Results First Posted: May 12, 2015

Record last verified: 2016-08

Locations

US (1)