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

January 4, 2017 updated by: Italo Biaggioni, Vanderbilt University Medical Center

Norepinephrine Transporter Blockade as a Pathophysiological 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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center (Harvard)
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10016
        • New York University
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

March 15, 2011

First Submitted That Met QC Criteria

March 15, 2011

First Posted (Estimate)

March 16, 2011

Study Record Updates

Last Update Posted (Estimate)

January 6, 2017

Last Update Submitted That Met QC Criteria

January 4, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 101311
  • U54NS065736 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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