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Atomoxetine and DAW2022 on OSA Severity

Primary Purpose

Obstructive Sleep Apnea

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo oral capsule
Atomoxetine Oral Capsule [Strattera]
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Moderate-to-severe OSA (AHI ≥ 15 events/hr)

Exclusion Criteria:

  • All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements.
  • Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
  • Use of SNRIs/SSRIs.
  • Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
  • Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:
  • Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
  • Hypersensitivity to the study drug (angioedema or urticaria)
  • Contraindications to DAW2020
  • Use of medications that lengthen QTc interval
  • Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease
  • Severe claustrophobia.

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo oral capsules

Atomoxetine and DAW2020 oral capsules

Arm Description

Placebo (2 pills) before sleep for a week

DAW2020 34 mg 4 h before sleep, single night administration for a week. Simultaneous administration of atomoxetine 40 mg for 3 days 30 min before sleep, 80 mg for the following 4 days, 30 min before sleep

Outcomes

Primary Outcome Measures

Effect of atomoxetine and DAW2020 on OSA severity
OSA severity will be quantified by the number of respiratory events/h (AHI)

Secondary Outcome Measures

Effect of atomoxetine and DAW2020 on arousal index
Arousal index will be calculated as the number of arousal per hour
Effect of atomoxetine and DAW2020 on nadir oxygen desaturation
Nadir oxygen desaturation will be calculated as the lowest oxygen saturation value during sleep

Full Information

First Posted
April 22, 2022
Last Updated
July 5, 2023
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05350215
Brief Title
Atomoxetine and DAW2022 on OSA Severity
Official Title
Effect of Atomoxetine and DAW2022 on OSA Severity
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2022 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. In previous research atomoxetine and oxybutynin showed promising effect at reducing OSA severity, however they reduced arousal threshold, one of the key traits responsible for OSA. Since oxybutynin was used mainly as a hypnotic, but it is burdened by several anti-cholinergic side effects, DAW2020, a hypnotic which prolonged the total sleep time in a previous trial in OSA patients, could be a better candidate to associate with atomoxetine.
Detailed Description
Two overnight sleep studies will be performed: a drug night and a placebo night, with a month of washout between treatments. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnography for monitoring sleep, physiological variables (endotypes), and respiratory events. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. The drugs will be administered as follows. There will be a 3-day run in of atomoxetine 40 mg followed by atomoxetine 80 mg starting on the fourth night until the night of the study. DAW2020 34 mg will be administered for 1-week to allow adequate plasma concentrations to be reached. For the sleep study, at least four hours of sleep (50% in the supine position) will be monitored to assess sleep and respiratory variables.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo oral capsules
Arm Type
Placebo Comparator
Arm Description
Placebo (2 pills) before sleep for a week
Arm Title
Atomoxetine and DAW2020 oral capsules
Arm Type
Active Comparator
Arm Description
DAW2020 34 mg 4 h before sleep, single night administration for a week. Simultaneous administration of atomoxetine 40 mg for 3 days 30 min before sleep, 80 mg for the following 4 days, 30 min before sleep
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo pills for a week, 1 pill 4 hr before sleep and 1 pill 30 min before sleep
Intervention Type
Drug
Intervention Name(s)
Atomoxetine Oral Capsule [Strattera]
Other Intervention Name(s)
DAW2020 Oral Capsule
Intervention Description
Atomoxetine for a week: 40 mg for 3 days 30 min before sleep, 80 mg for 4 days 30 min before sleep Simultaneous administration of DAW2020 for a week, 34 mg 4 h before sleep
Primary Outcome Measure Information:
Title
Effect of atomoxetine and DAW2020 on OSA severity
Description
OSA severity will be quantified by the number of respiratory events/h (AHI)
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Effect of atomoxetine and DAW2020 on arousal index
Description
Arousal index will be calculated as the number of arousal per hour
Time Frame
1 week
Title
Effect of atomoxetine and DAW2020 on nadir oxygen desaturation
Description
Nadir oxygen desaturation will be calculated as the lowest oxygen saturation value during sleep
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Moderate-to-severe OSA (AHI ≥ 15 events/hr) Exclusion Criteria: All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements. Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid). Use of SNRIs/SSRIs. Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition. Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea: Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias. Hypersensitivity to the study drug (angioedema or urticaria) Contraindications to DAW2020 Use of medications that lengthen QTc interval Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease Severe claustrophobia.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ludovico Messineo, MD, PhD
Phone
18572726188
Email
lmessineo@bwh.harvard.edu
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02135
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicole Calianese
Phone
617-732-8976
Email
ncalianese@partners.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Atomoxetine and DAW2022 on OSA Severity

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