A Phase 4 interventional study of Northera and Placebo in Hypotension, Orthostatic, Hypotension and Spinal Cord Injuries, sponsored by James J. Peters Veterans Affairs Medical Center. Completed at 2 sites in United States. Open to participants aged 18 Years to 89 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-07.
Sponsored by James J. Peters Veterans Affairs Medical Center · Phase 4, Interventional, and Treatment
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.
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.
1,948 studies on the registry are indexed under Spinal Cord Injuries; 505 are open to participants now.
This study's enrollment of 22 is close to the median of 24 across 1,566 interventional studies indexed under Spinal Cord Injuries.
Browse Spinal Cord Injuries studies →James J. Peters Veterans Affairs Medical Center is the lead sponsor of 49 studies on the registry; 4 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 2 (25%) have results posted.
Counted across the registry records on this site, refreshed daily.
Study 1:
SCI Subjects (n=40):
Low Blood Pressure:
Able to provide informed consent
Study 2:
SCI Subjects (n=40):
Low Blood Pressure:
Exclusion Criteria:
Individuals with frequent or severe autonomic dysreflexia:
Your prescription medications will be reviewed by the study investigators and research staff. If you are currently taking medications to treat any of the following please make the investigators aware:
d. Depression, Schizophrenia, Attention Deficit Hyperactivity Disorder (ADHD) e. Pain (opioids) f. Infection or illness (antibiotics) g. Erectile dysfunction (Viagra, Cialis, etc.) h. Overactive bladder i. High or low blood pressure j. Migraine headaches k. Malaria l. asthma
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Drug: Northera
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
Drug: Northera · Other: Placebo
Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
Also known as: Droxidopa
Study 2 is blinded placebo controlled trial using the individualized optimal dose of droxidopa determined by study 1.
Proportion of Systolic BP Within a Normotensive Range
To determine the proportion (%) of normotensive systolic blood pressure for males=(110-120 mmHg); and females=(101-120 mmHg) following administration of droxidopa.
Time frame: up to 240 minutes following administration of droxidopa
Supine Systolic Blood Pressure
To measure supine systolic blood pressure following administration of droxidopa compared to placebo in hypotensive participants with SCI
Time frame: within 60 minutes of administration of droxidopa or placebo
Orthostatic Systolic Blood Pressure
To document systolic blood pressure responses to head-up tilt to 70 degrees following administration of droxidopa compared to placebo in hypotensive participants with SCI.
Time frame: 60-90 minutes following administration of droxidopa or placebo
Orthostatic Cerebral Blood Flow
To compare cerebral blood flow velocity in the middle cerebral artery following administration of placebo compared to administration of Northera (Droxidopa)
Time frame: 60-90 minutes following administration of droxidopa or placebo
| Milestone | Study 1: Dose Optimization of Northera | Study 2: Blinded Placebo/Northera | Study 2: Blinded Northera/Placebo |
|---|---|---|---|
| Started | 15 | 4 | 2 |
| Completed | 13 | 4 | 2 |
| Not completed | 2 | 0 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 | 0 |
To determine the proportion (%) of normotensive systolic blood pressure for males=(110-120 mmHg); and females=(101-120 mmHg) following administration of droxidopa.
| Systolic Blood Pressure Recordings | Study 1: Dose Optimization of Northera | Study 2: Placebo | Study 2: Northera |
|---|---|---|---|
| Proportion of Systolic BP Within a Normotensive Range | 167 | 117 | 89 |
To measure supine systolic blood pressure following administration of droxidopa compared to placebo in hypotensive participants with SCI
| mmHg | Study 1: Dose Optimization Northera | Study 2: Placebo | Study 2: Northera |
|---|---|---|---|
| Supine Systolic Blood Pressure | 99.9 ± 12.3 | 110.9 ± 10.8 | 107.9 ± 8.7 |
To document systolic blood pressure responses to head-up tilt to 70 degrees following administration of droxidopa compared to placebo in hypotensive participants with SCI.
| mmHg | Study 1: Dose Optimization Northera | Study 2: Placebo | Study 2: Northera |
|---|---|---|---|
| Orthostatic Systolic Blood Pressure | — | 99.92 ± 11.03 | 91.99 ± 9.85 |
To compare cerebral blood flow velocity in the middle cerebral artery following administration of placebo compared to administration of Northera (Droxidopa)
| cm/sec | Study 1: Dose Optimization of Northera | Study 2: Placebo | Study 2: Northera |
|---|---|---|---|
| Orthostatic Cerebral Blood Flow | — | 36.4 ± 7.23 | 36.8 ± 5.26 |
Collected over 2 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Study 1: Dose Optimization of Northera | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) |
| Study 2: Northera | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) |
| Study 2: Placebo | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) |
| Age, Categorical(Participants) | Study 1: Dose Optimization of Northera | Study 2: Blinded Placebo/Northera | Study 2: Blinded Northera/Placebo | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 13 | 4 | 2 | 19 |
| >=65 years | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Study 1: Dose Optimization of Northera | Study 2: Blinded Placebo/Northera | Study 2: Blinded Northera/Placebo | Total |
|---|---|---|---|---|
| Mean | 42.54 ± 9.9 | 41 ± 13 | 37 ± 2 | 40.65 ± 10.20 |
| Sex: Female, Male(Participants) | Study 1: Dose Optimization of Northera | Study 2: Blinded Placebo/Northera | Study 2: Blinded Northera/Placebo | Total |
|---|---|---|---|---|
| Female | 4 | 0 | 0 | 4 |
| Male | 9 | 4 | 2 | 15 |
| Race (NIH/OMB)(Participants) | Study 1: Dose Optimization of Northera | Study 2: Blinded Placebo/Northera | Study 2: Blinded Northera/Placebo | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 1 | 0 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 0 | 1 |
| White | 11 | 1 | 1 | 13 |
| More than one race | 0 | 3 | 1 | 4 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Study 1: Dose Optimization of Northera | Study 2: Blinded Placebo/Northera | Study 2: Blinded Northera/Placebo | Total |
|---|---|---|---|---|
| United States | 13 | 4 | 2 | 19 |
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James J. Peters Veterans Affairs Medical Center