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Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension (6103)

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ClinicalTrials.gov Identifier: NCT01316666
Recruitment Status : Completed
First Posted : March 16, 2011
Last Update Posted : January 6, 2017
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University

Brief Summary:
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.

Condition or disease
Orthostatic Hypotension Pure Autonomic Failure Multiple System Atrophy Parkinson's Disease

Detailed Description:
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.

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Study Type : Observational
Actual Enrollment : 50 participants
Time Perspective: Prospective
Official Title: Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension
Study Start Date : March 2011
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Neurogenic Hypotension
Patients with neurogenic hypotension, which includes those with Pure Autonomic Failure (PAF), Multiple System Atrophy (MSA) and Parkinson Disease (PD)

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
participants with neurogenic orthostatic hypotension, which is a drop in systolic blood pressure of at least 30 mmHg within 5 minutes of standing with associated impaired autonomic reflexes.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01316666

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United States, Massachusetts
Beth Israel Deaconess Medical Center (Harvard)
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55902
United States, New York
New York University
New York, New York, United States, 10016
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Italo Biaggioni, MD Vanderbilt University
Additional Information:

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Responsible Party: Italo Biaggioni, MD, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01316666    
Other Study ID Numbers: 101311
U54NS065736 ( U.S. NIH Grant/Contract )
First Posted: March 16, 2011    Key Record Dates
Last Update Posted: January 6, 2017
Last Verified: January 2017
Keywords provided by Italo Biaggioni, Vanderbilt University:
orthostatic hypotension
Multiple System Atrophy
Pure Autonomic Failure
Parkinson's Disease
Additional relevant MeSH terms:
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Parkinson Disease
Multiple System Atrophy
Shy-Drager Syndrome
Hypotension, Orthostatic
Pure Autonomic Failure
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pathological Conditions, Anatomical
Vascular Diseases
Cardiovascular Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Orthostatic Intolerance