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A Novel Pharmacological Therapy for Obstructive Sleep Apnea

Primary Purpose

Sleep Apnea

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Atomoxetine
Oxybutynin
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea

Eligibility Criteria

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

Inclusion criteria:

  • Ages 21-70 years
  • Diagnosed OSA or clinically-suspected OSA
  • Not using CPAP (>1 month).

Exclusion criteria:

  • Any uncontrolled medical condition
  • Current use of the medications under investigation
  • Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
  • Current use of hypnotic medications (trazodone, eszopiclone, benzodiazepines).
  • Current use of SNRIs/SSRIs or anticholinergic medications.
  • Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
  • Respiratory disorders other than sleep disordered breathing:

chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

  • Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.

  • Contraindications for atomoxetine and oxybutynin, including:

    • hypersensitivity to study drugs (angioedema or urticaria)
    • pheochromocytoma
    • use of monoamine oxidase inhibitors
    • benign prostatic hypertrophy, urinary retention
    • untreated narrow angle glaucoma
    • bipolar disorder, mania, psychosis
    • history of major depressive disorder (age<24).
    • history of attempted suicide or suicidal ideation within one year prior to screening
    • clinically significant constipation, gastric retention
    • pre-existing seizure disorders
    • clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)
    • clinically-significant liver disorders
    • clinically-significant cardiovascular conditions
    • severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline)
    • cardiomyopathy (LVEF<50%) or heart failure
    • advanced atherosclerosis
    • history of cerebrovascular events
    • history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation
    • other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate
    • myasthenia gravis
    • pregnancy/breast-feeding
  • Allergy to lidocaine (Aim 2 only)
  • Claustrophobia
  • Pregnancy or nursing

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Atomoxetine and Oxybutynin

Placebo

Arm Description

Participants will take Atomoxetine and Oxybutynin nightly for one month. Half doses will be given on the first three nights.

Participants will take Placebos nightly for one month. Half doses will be given on the first three nights.

Outcomes

Primary Outcome Measures

Apnea-hypopnea index [AHI]
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline

Secondary Outcome Measures

Hypoxic Burden
Desaturation area under curve × event frequency
Arousal index
Scored EEG arousals per hour (>3 s), % change from baseline
Epworth Sleepiness Scale
Self-reported sleepiness on scale of 0-24, higher being more sleepy
Functional Outcomes of Sleep Questionnaire, Short Form
Disease-specific quality of life
Sleep Apnea Quality of Life Index, Short Form
Disease-specific quality of life

Full Information

First Posted
April 16, 2019
Last Updated
October 16, 2023
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03919955
Brief Title
A Novel Pharmacological Therapy for Obstructive Sleep Apnea
Official Title
A Novel Pharmacological Therapy for Obstructive Sleep Apnea
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 3, 2019 (Actual)
Primary Completion Date
October 20, 2023 (Anticipated)
Study Completion Date
October 20, 2023 (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.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A pharmacological, non-mechanical therapy for OSA that is efficacious and tolerable remains elusive. Here the investigators study the effect on sleep apnea severity of a combination of pharmacological agents (atomoxetine and oxybutynin, "AtoOxy") over a 1 month period of time. The current study will answer the following questions: Does ongoing, repeated-dose administration of atomoxetine-plus-oxybutynin (referred to as "AtoOxy") improve OSA severity, and do patients exhibit signs of symptomatic relief? Most importantly, which phenotypic subgroup of patients preferentially benefit from this intervention?
Detailed Description
Aim 1 - Effect of AtoOxy on sleep apnea severity. In a randomized controlled double-blind crossover study, 48 patients with moderate-to-severe OSA will take atomoxetine-plus-oxybutynin ("AtoOxy") versus placebo nightly for 1 month, with a 2-week washout in between. The investigators will test the hypothesis that AtoOxy reduces the Apnea-hypopnea index (primary outcome measure), and improves the following secondary outcomes: Nocturnal oxygenation, per "hypoxic burden of sleep apnea" Frequency of arousals from sleep (Arousal index) Self-reported sleepiness (Epworth Sleepiness Scale) Disease-specific quality of life (Functional Outcomes of Sleep Questionnaire, Short Form). Disease-specific quality of life (Sleep Apnea Quality of Life Index, Short Form) Additional pre-specified exploratory outcome measures will be assessed, including Visual Analog Scales (Sleep Quality, Treatment Satisfaction) and additional polysomnographic measures of sleep (Stage 1 sleep, %total sleep time). Adherence and adverse events will also be carefully monitored to assess repeated-dose tolerance of the intervention. Aim 2 - Determine which patient phenotypes respond best to AtoOxy. Patients will also take part in an additional night before initiating study medication to measure the key mechanisms causing OSA. The investigators will prospectively test the hypothesis that greater pharyngeal collapsibility determines a reduced response to therapy. They will also separately test the hypotheses that a reduced muscle responsiveness, reduced baseline muscle activation, a higher arousal threshold, and a lower loop gain will facilitate a greater response to therapy.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Atomoxetine and Oxybutynin
Arm Type
Experimental
Arm Description
Participants will take Atomoxetine and Oxybutynin nightly for one month. Half doses will be given on the first three nights.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will take Placebos nightly for one month. Half doses will be given on the first three nights.
Intervention Type
Drug
Intervention Name(s)
Atomoxetine
Other Intervention Name(s)
Strattera
Intervention Description
Atomoxetine 80 mg, per mouth, before bed
Intervention Type
Drug
Intervention Name(s)
Oxybutynin
Other Intervention Name(s)
Ditropan
Intervention Description
Oxybutynin 5 mg, per mouth, before bed
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, per mouth, before bed
Primary Outcome Measure Information:
Title
Apnea-hypopnea index [AHI]
Description
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline
Time Frame
one month
Secondary Outcome Measure Information:
Title
Hypoxic Burden
Description
Desaturation area under curve × event frequency
Time Frame
one month
Title
Arousal index
Description
Scored EEG arousals per hour (>3 s), % change from baseline
Time Frame
one month
Title
Epworth Sleepiness Scale
Description
Self-reported sleepiness on scale of 0-24, higher being more sleepy
Time Frame
one month
Title
Functional Outcomes of Sleep Questionnaire, Short Form
Description
Disease-specific quality of life
Time Frame
one month
Title
Sleep Apnea Quality of Life Index, Short Form
Description
Disease-specific quality of life
Time Frame
one month

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: Ages 21-70 years Diagnosed OSA or clinically-suspected OSA Not using CPAP (>1 month). Exclusion criteria: Any uncontrolled medical condition Current use of the medications under investigation Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid). Current use of hypnotic medications (trazodone, eszopiclone, benzodiazepines). Current use of SNRIs/SSRIs or anticholinergic medications. Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition. Respiratory disorders other than sleep disordered breathing: chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions. Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias. Contraindications for atomoxetine and oxybutynin, including: hypersensitivity to study drugs (angioedema or urticaria) pheochromocytoma use of monoamine oxidase inhibitors benign prostatic hypertrophy, urinary retention untreated narrow angle glaucoma bipolar disorder, mania, psychosis history of major depressive disorder (age<24). history of attempted suicide or suicidal ideation within one year prior to screening clinically significant constipation, gastric retention pre-existing seizure disorders clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2) clinically-significant liver disorders clinically-significant cardiovascular conditions severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline) cardiomyopathy (LVEF<50%) or heart failure advanced atherosclerosis history of cerebrovascular events history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate myasthenia gravis pregnancy/breast-feeding Allergy to lidocaine (Aim 2 only) Claustrophobia Pregnancy or nursing
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Scott A Sands, PhD
Phone
6172780911
Email
sasands@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott A Sands, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Hess
Phone
617-732-8976
Email
lhess1@bwh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD collected during the study, after deidentification, will be available immediately after publication to researchers who provide a methodologically sound proposal for any purpose.
IPD Sharing Time Frame
Immediately after publication. No end date.
IPD Sharing Access Criteria
1-page proposals should be directed to Dr. Scott Sands (sasands@bwh.harvard.edu). To gain access, requestors will be asked to sign a data use agreement.

Learn more about this trial

A Novel Pharmacological Therapy for Obstructive Sleep Apnea

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