NCT02908529

Brief Summary

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal subjects. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of atomoxetine (a norepinephrine reuptake inhibitor) and oxybutynin (an antimuscarinic drug) administered together on OSA phenotype traits and OSA severity during sleep.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Sep 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2016

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

September 14, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 21, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2017

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

January 29, 2019

Completed
Last Updated

January 29, 2019

Status Verified

January 1, 2019

Enrollment Period

1.2 years

First QC Date

September 14, 2016

Results QC Date

November 16, 2018

Last Update Submit

January 10, 2019

Conditions

Obstructive Sleep Apnea (OSA)

Outcome Measures

Primary Outcomes (1)

  • Apnea Hypopnea Index (AHI, Events/Hour of Sleep)

    Based on previous studies the investigators anticipate that Atomoxetine and Oxybutynin will reduce AHI more effectively in subjects with moderate sleep apnea, mildly obese (BMI\<32), Vpassive \> 50% of Veupnea (ventilation during eupneic ventilatory drive), low muscle compensation (Vactive - Vpassive \<1 L/min)

    1 night

Secondary Outcomes (1)

  • Genioglossus Muscle Responsiveness to Increased Ventilatory Drive (Esophageal Pressure Swings)

    1 night

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo 2 hours before bedtime

Drug: Placebo, 2 tablets

Combination product of Atomoxetine and Oxybutynin

ACTIVE COMPARATOR

Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep

Drug: Combination product of Atomoxetine and Oxybutynin

Interventions

Combination product of Atomoxetine and OxybutyninDRUG

Combination product of Atomoxetine 80 mg and Oxybutynin 5 mg 2 hours before sleep

Also known as: Strattera + Ditropan
Combination product of Atomoxetine and Oxybutynin
Placebo, 2 tabletsDRUG

Placebo 2 tablets 2 hours before sleep

Placebo

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may not qualify if:

  • Any medical condition other than well controlled hypertension.
  • Any medication known to influence breathing, sleep/arousal or muscle physiology.
  • Claustrophobia.
  • Inability to sleep supine.
  • Allergy to lidocaine, Oxymetazoline HCl, atomoxetine/oxybutynin.
  • Individuals with underlying cardiac disease, such as arrhythmias.
  • Individuals taking psychiatric medications, such as atomoxetine, or any of the studied medications for medical care.
  • History of seizures
  • For women: Pregnancy.
  • History of panic disorder / hyperventilation syndrome / Attention deficit-hyperactivity disorder (ADHD) / autism

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sleep Disorders Research Program Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

  • Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, Eckert DJ, White DP, Wellman A. The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial. Am J Respir Crit Care Med. 2019 May 15;199(10):1267-1276. doi: 10.1164/rccm.201808-1493OC.

    PMID: 30395486DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

oxybutyninAtomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Sleep Apnea SyndromesApneaRespiration DisordersRespiratory Tract DiseasesSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System Diseases

Intervention Hierarchy (Ancestors)

PropylaminesAminesOrganic Chemicals

Results Point of Contact

Title
Luigi Taranto Montemurro, MD
Organization
Brigham and women's Hospital
ltarantomontemurro@bwh.harvard.edu
6177326541

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
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
Assistant Professor of Medicine - Harvard Medical School

Study Record Dates

First Submitted

September 14, 2016

First Posted

September 21, 2016

Study Start

September 1, 2016

Primary Completion

December 1, 2017

Study Completion

January 1, 2018

Last Updated

January 29, 2019

Results First Posted

January 29, 2019

Record last verified: 2019-01

Data Sharing

IPD Sharing
Will share

Locations

US(1)