Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title: Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury

Status Completed

Clinical Trial Summary

The goal of this study is to determine the efficacy of the drug Droxidopa (Northera) in increasing blood pressure in subject with hypotension, low blood pressure, which is classified as blood pressure less than 110/70 in males and 100/70 in females. The first aim is to determine the proportion of subject with Spinal Cord Injury (SCI) who have a normotensive response to Droxidopa. The second is to determine the proportion of subject with SCI who express a hypertensive response to Droxidopa. A Normal blood pressure ranges from 111-139 in males and 101-139 in females and a hypertensive blood pressure is anything higher than 140 in males and females.

The study would take place in James J. Peters VA Medical Center (JJPVAMC) and The Icahn School of Medicine at Mount Sinai (ISMMS) in Manhattan, New York.

Clinical Trial Description

Interruption of sympathetic cardiovascular autonomic regulation following spinal cord injury (SCI) is associated with significantly reduced plasma norepinephrine (NE) levels, hypotension and orthostatic hypotension (OH), particularly in individuals with high cord lesions. Although the incidence of hypotension is reported to be as high as 70% in persons with cervical lesions (i.e., tetraplegia), the vast majority of these individuals remains asymptomatic and, therefore, does not raise clinical concern, or prompt intervention. While it is appreciated that clinicians are faced with substantial challenges in managing blood pressure (BP) in persons with SCI, contrary to the prevailing belief, asymptomatic hypotension and OH are not benign conditions. Reports suggest that asymptomatic hypotensive individuals with SCI may have subclinical cognitive dysfunction affecting memory and attention processing and increased incidence of fatigue and depression compared to normotensive individuals with SCI. It must be appreciated that to date, there are no FDA approved pharmaceutical options proven to be safe and effective for treatment of hypotension and OH in the SCI population. Until 2014, midodrine hydrochloride was the only agent with FDA approval for treatment of symptomatic neurogenic OH (NOH). Midodrine, an alpha-agonist, is the most commonly prescribed agent used to treat symptomatic hypotension in the SCI population despite a lack of convincing evidence of safety or efficacy. In 2014 droxidopa (L-threo-3,4-dihydroxyphenylserine - NORTHERA; Chelsea Therapeutics, Charlotte, NC) was approved by the FDA for treatment of symptomatic NOH based on data collected in conditions of autonomic dysfunction. Droxidopa is a NE precursor that is stored in neuronal and non-neuronal tissue and has been shown to increase standing BP and reduce symptoms of orthostatic intolerance in individuals with symptomatic NOH. We recently reported preliminary evidence of a mean increase in seated BP in individuals with SCI following oral administration of 400 mg of droxidopa; however, this dose was effective in only 5 of the 10 subjects tested and the BP effect waned over a 4-hour observation. Because of its unique pharmacokinetic profile, droxidopa is a highly promising agent to treat hypotension in persons with SCI. As such; there exists a pressing imperative to determine the clinical value and safety of droxidopa in hypotensive individuals with SCI. ;

Related Conditions & MeSH terms

• Hypotension
• Hypotension, Orthostatic
• Spinal Cord Injuries
• Wounds and Injuries

• NCT number: NCT03602014
• Study type: Interventional
• Source: James J. Peters Veterans Affairs Medical Center
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2018
• Completion date: December 31, 2021