Norepinephrine Transporter Blockade, Autonomic Failure (NETAF)

NCT02784535 | Completed Phase 2 Results DMC

• 1 other identifier: 160415
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Neurogenic Orthostatic Hypotension

Keywords

norepinephrine transporter inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in the OHQ (Orthostatic Hypotension Questionnaire) Composite Score

  The Orthostatic Hypotension Questionnaire (OHQ) , patient-reported assessment tool consisting of the OH Symptom Assessment (OHSA), OH Daily Activity Scale (OHDAS). The composite score 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 daily activities, the Orthostatic Hypotension Daily Activity Scale (OHDAS). This scales helps to measure the impact of orthostatic symptoms on daily. Scale is between 0-10: where "0" is minimum Orthostatic symptoms and "10" is the maximum / worse possible severity of the symptoms. All items are scored 0 through 10 (higher scores = more impact) and summed into the respective total scores. The OHSA and OHDAS subscales averaged to compute the OHQ composite score.

  week 0 to week 4

Secondary Outcomes (2)

• Change in Blood Pressure

  Baseline to 4 weeks

• Change in Heart Rate (HR)

  Baseline and at 4 weeks

Study Arms (2)

placebo

PLACEBO COMPARATOR

placebo capsules

Drug: Atomoxetine

atomoxetine

ACTIVE COMPARATOR

atomoxetine capsules 10 mg or 18 mg

Drug: Placebo

Interventions

Atomoxetine DRUG

norepinephrine transporter inhibitor

Also known as: strattera

placebo

Placebo DRUG

placebo

Also known as: non active medication

atomoxetine

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• NYU Langone Health: collaborator

Study Sites (2)

Dysautonomic Center at NYU Langone Medical Center

New York, New York, 10016, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• Ramirez CE, Okamoto LE, Arnold AC, Gamboa A, Diedrich A, Choi L, Raj SR, Robertson D, Biaggioni I, Shibao CA. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2014 Dec;64(6):1235-40. doi: 10.1161/HYPERTENSIONAHA.114.04225. Epub 2014 Sep 2.

  PMID: 25185131 BACKGROUND

• Shibao C, Raj SR, Gamboa A, Diedrich A, Choi L, Black BK, Robertson D, Biaggioni I. Norepinephrine transporter blockade with atomoxetine induces hypertension in patients with impaired autonomic function. Hypertension. 2007 Jul;50(1):47-53. doi: 10.1161/HYPERTENSIONAHA.107.089961. Epub 2007 May 21.

  PMID: 17515448 BACKGROUND

MeSH Terms

Interventions

Atomoxetine Hydrochloride

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr Cyndya Shibao
• Organization: Vanderbilt University Medical center

cyndya.shibao@vumc.org

615-322-2318

Study Officials

• Cyndya A Shibao, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Horacio Kaufmann, MD

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: May 27, 2016
• Study Start: August 29, 2016
• Primary Completion: May 12, 2021
• Study Completion: June 1, 2023
• Last Updated: September 13, 2023
• Results First Posted: September 16, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)