Norepinephrine Transporter Blockade, Autonomic Failure

• Status: Completed
• Trial end date: 2021-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Collaborator: Vanderbilt University Medical Center
• Treatments: Norepinephrine

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