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Norepinephrine Transporter Blockade, Autonomic Failure

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ClinicalTrials.gov Identifier: NCT02796209
Recruitment Status : Recruiting
First Posted : June 10, 2016
Last Update Posted : October 19, 2018
Sponsor:
Collaborator:
Vanderbilt University Medical Center
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:

Atomoxetine, a selective norepinephrine transporter (NET) blocker, increases standing blood pressure and improves neurogenic orthostatic hypotension (NOH)-related symptoms to a greater extent than midodrine, the current standard of care. Atomoxetine could be a new therapeutic alternative for the treatment of NOH in patients with autonomic failure, particularly those with multiple system atrophy (MSA).

The proposed study consists of an open-label, dose-optimization phase followed by a randomized, double-blind, placebo-controlled, 2x2 crossover phase.


Condition or disease Intervention/treatment Phase
Multiple System Atrophy (MSA) Drug: Atomexetine Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Phase 2 Norepinephrine Transporter Blockade, Autonomic Failure
Study Start Date : May 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Atomexetine
Following the dose optimization phase, investigators will stratify the treatment assignment by Atomexetine dose (10mg or 19mg twice a day)
Drug: Atomexetine
Upon completion of the 4-week treatment period (period 1), the investigator or research nurse will instruct the subject to discontinue the study medication for 1 week (wash-out period). After this period, the subject will complete the second 4-week treatment period (period 2).

Placebo Comparator: Placebo
The placebo capsules will be of identical color, size, and approximate weight to provide an authentic blinded effect. The capsule contents will be a microcrystalline cellulose, NF (PH-105), which should not produce any adverse effects. It is a common pharmaceutical capsule filler used in the industry.
Drug: Placebo
Upon completion of the 4-week treatment period (period 1), the investigator or research nurse will instruct the subject to discontinue the study medication for 1 week (wash-out period). After this period, the subject will complete the second 4-week treatment period (period 2).




Primary Outcome Measures :
  1. Change from Baseline of Orthostatic Hypotension Questionnaire (OHQ) Score [ Time Frame: Days 0, 14, 28, 36, 50, and 64 ]
    The OHQ is composed of 10 individual items: 6 items measure specific symptoms (the Orthostatic Hypotension Symptom Assessment [OHSA]), and 4 items measure the impact of those symptoms on a patient's daily activities (the Orthostatic Hypotension Daily Activity Scale [OHDAS])



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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neurogenic Orthostatic Hypotension (defined by a reduction of ≥30 mmHg drop in SBP within 3 minutes of standing, associated with impaired autonomic reflexes as assessed by autonomic function tests.

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Hypersensitivity to atomoxetine (severe allergic reaction, rash, urticaria, anaphylaxis)
  • Use of other norepinephrine transporter inhibitors such as Wellbutrin (Bupropion), Cymbalta (Duloxetine), Effexor (venlafaxine), Pristiq (desvenlafaxine), Savella (milnacipran)
  • Previous history (within 14 days prior to enrollment) and current use of monoamine oxidase inhibitors
  • Concomitant use of strong CYP2D6 inhibitors such as delavirdine, paroxetine, fluoxetine, quinidine
  • Pre-existing sustained severe hypertension (BP 140/80 mmhg in the sitting position)
  • Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >2 x upper limit of normal range)
  • Impaired renal function (serum creatinine equal or more than 1.6 mg/dl)
  • Myocardial infarction within 6 months prior to enrollment
  • Congestive heart failure (LV hypertrophy acceptable)
  • History of serious neurologic disease such as cerebral hemorrhage, or stroke
  • Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, unlikelihood of completing the study, and mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study
  • Patients with narrow angle glaucoma
  • Patients with or a history of pheochromocytoma

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): NCT02796209


Contacts
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Contact: Jose Martinez martij34@nyumc.org

Locations
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United States, New York
New York University School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Jose Martinez       martij34@nyumc.org   
Principal Investigator: Horacio Kaufman, MD         
Sponsors and Collaborators
NYU Langone Health
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Horacio Kaufman, MD New York University Medical School

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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT02796209     History of Changes
Other Study ID Numbers: 16-00453
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
Keywords provided by NYU Langone Health:
atomoxetine
autonomic failure
Additional relevant MeSH terms:
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Multiple System Atrophy
Shy-Drager Syndrome
Brain Diseases
Pure Autonomic Failure
Atrophy
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Norepinephrine
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents