Norepinephrine Transporter Blockade, Autonomic Failure

Multiple System Atrophy (MSA) Clinical Trial

Official title:

Phase 2 Norepinephrine Transporter Blockade, Autonomic Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02796209
• Other study ID #: 16-00453
• Status: Completed
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: May 1, 2021

Study information

• Verified date: January 2022
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 1, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple System Atrophy
• Multiple System Atrophy (MSA)
• Pure Autonomic Failure
• Shy-Drager Syndrome

Intervention

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
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).

Locations

Country	Name	City	State
United States	New York University School of Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline of Orthostatic Hypotension Questionnaire (OHQ) Score	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]). Each item in the OHSA section is scored from 0 (none) to 10 (worst possible). Each item in OHDAS is scored from 0 (no interference) to 10 (total interference). The total score range is 0-100; the higher the score, the more severe the symptoms and more interference with daily life.	Day 0, Day 14
Primary	Change from Baseline of Orthostatic Hypotension Questionnaire (OHQ) Score	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]). Each item in the OHSA section is scored from 0 (none) to 10 (worst possible). Each item in OHDAS is scored from 0 (no interference) to 10 (total interference). The total score range is 0-100; the higher the score, the more severe the symptoms and more interference with daily life.	Day 0, Day 28
Primary	Change from Baseline of Orthostatic Hypotension Questionnaire (OHQ) Score	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]). Each item in the OHSA section is scored from 0 (none) to 10 (worst possible). Each item in OHDAS is scored from 0 (no interference) to 10 (total interference). The total score range is 0-100; the higher the score, the more severe the symptoms and more interference with daily life.	Day 0, Day 64