Norepinephrine Transporter Blockade, Autonomic Failure (NETAF)

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Drug therapy for patients suffering from autonomic failure and neurogenic orthostatic hypotension are scarce and not effective. If left untreated, these patients have the highest risk of syncope, falls and fall-related injuries. The proposed study will determine the clinical benefit of a commercially available drug, atomoxetine, to reduce symptoms associated with neurogenic orthostatic hypotension in patients with autonomic failure.

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

Details

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

Criteria

Inclusion Criteria:

• 40 years old or older

• Neurogenic Orthostatic Hypotension (defined by a reduction of ≥20 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

• Narrow-angle glaucoma