Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension

NCT ID: NCT01316666

Last Updated: 2017-01-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2016-12-31

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.

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.

Conditions

Orthostatic Hypotension; Pure Autonomic Failure; Multiple System Atrophy; Parkinson's Disease

Study Design

• Study Time Perspective: PROSPECTIVE

Study Groups

Neurogenic Hypotension

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

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Italo Biaggioni

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Italo Biaggioni, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Beth Israel Deaconess Medical Center (Harvard)

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

New York University

New York, New York, United States

Vanderbilt University

Nashville, Tennessee, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 2012253 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 9869555 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Goldstein DS, Polinsky RJ, Garty M, Robertson D, Brown RT, Biaggioni I, Stull R, Kopin IJ. Patterns of plasma levels of catechols in neurogenic orthostatic hypotension. Ann Neurol. 1989 Oct;26(4):558-63. doi: 10.1002/ana.410260410.

Reference Type: BACKGROUND

PMID: 2510587 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 12736730 (View on PubMed)

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Reference Type: BACKGROUND

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Related Links

http://www.bidmc.org/CentersandDepartments/Departments/Neurology.aspx

Beth Israel Deaconess Medical Center Department of Neurology

Other Identifiers

U54NS065736

Identifier Type: NIH

Identifier Source: secondary_id

View Link

101311

Identifier Type: -

Identifier Source: org_study_id