Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension

The autonomic or automatic nervous system helps control blood pressure. Diseases of the autonomic nervous system may result in a drop in blood pressure on standing in many cases leading to fainting. Diseases that affect the autonomic nervous system include pure autonomic failure, multiple system atrophy and Parkinson's disease, and can present with very similar symptoms and it is sometimes difficult to determine an exact diagnosis. The purpose of the study is to find out if the blood pressure response from taking a single dose of the medication atomoxetine can help in the diagnosis of these diseases.

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Key information

Conditions

Orthostatic Hypotension Autonomic Nervous System Diseases Basal Ganglia Diseases Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Hypotension Hypotension, Orthostatic Movement Disorders Multiple System Atrophy Nervous System Diseases Neurodegenerative Diseases Orthostatic Intolerance Parkinson Disease Parkinson's Disease Parkinsonian Disorders Primary Dysautonomias Pure Autonomic Failure Synucleinopathies Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Beth Israel Deaconess Medical Center (Harvard), Boston, Massachusetts, United States

About this study

This is an observational, prospective three-year longitudinal study. The investigators will enroll participants with primary neurogenic orthostatic hypotension. All participants will undergo an extensive neurological and cardiovascular evaluation, including detailed autonomic testing and quality of life assessment. The investigators will then determine the magnitude of the pressor effect produced by 18 mg atomoxetine given orally, measured 1 hour after drug administration. Participants will be followed annually or more often if there is a significant change in their clinical condition. During follow up at year 3, the investigators will repeat the initial neurological, cardiovascular and autonomic evaluation. The primary endpoint would be the final diagnosis made at year 3 after the initial evaluation (at the end of the follow-up period) or if they develop significant worsening of symptoms during follow-up phone assessments, based on specific clinical criteria.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Age 18-80 years old with Neurogenic orthostatic hypotension, ≥30 mmHg drop in SBP within 5 minutes of standing
Associated with impaired autonomic reflexes, as determined by absence of blood pressure overshoot during phase IV of the Valsalva maneuver
Absence of other identifiable causes of autonomic neuropathy
Able and willing to provide informed consent

Exclusion criteria

Pregnancy
Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies
Known intolerance to atomoxetine, Pre-existing sustained severe hypertension (BP at least 180/110 mmHg in the sitting position)
Clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months
Any other significant systemic, hepatic, cardiac or renal illness
Use of MAO-I within 14 days
Known closed-angle glaucoma or Life-threatening arrhythmias

Treatment and study plan

Primary outcomes

Final Diagnosis (pre vs post ganglionic autonomic failure) based on clinical criteria.

Time frame: 3 years

Probable MSA - PAF with urinary incontinence or an orthostatic decrease of 30 mmHG in systolic blood pressure within 3 minutes of standing and poorly levodopa responsive parkinsonism or a cerebellar syndome.

For Possible MSA - parkinsonism or a cerebellar syndrome and one additional feature.

Probable PAF - orthostatic hypotension and impaired autonomic reflexes in the absence of clinical signs or symptoms of neurodegeneration.

For Parkinson's Disease: diagnosed based on the United Kingdom Parkinson Disease Society Brain Bank clinical diagnostic criteria.

Sponsors and collaborators

Lead sponsor

Vanderbilt University Medical Center

Other

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension

Acronym: 6103

Important dates

Study start: 2011
Primary completion: 2016
Study completion: 2016
First posted: Mar 16, 2011
Registry last updated: Jan 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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