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Identifying Sleep Apnea Patients That Best Respond to Atomoxetine Plus Oxybutynin Therapy

Primary Purpose

Obstructive Sleep Apnea

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atomoxetine
Oxybutynin
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:

  • Suspected or diagnosed OSA
  • Recent drug induced sleep endoscopy results available (performed as part of routine clinical care).

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, narcolepsy, or parasomnias.
  • Contraindications for atomoxetine and oxybutynin, including:

    • hypersensitivity to atomoxetine or oxybutynin (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
    • moderate-to-severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline; average of evening and morning measures*)
    • 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
  • Claustrophobia
  • Pregnancy or nursing

    n.b. Development of new hypertension that is recognized on the final day of study medications during outcomes collection will not be used as stopping criteria for discontinuing outcomes collection.

Participants that are sexually active and able to become pregnant must agree to use birth control for the entire study.

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

AtoOxy Predicted Responders

AtoOxy Predicted Nonresponders

Arm Description

Participants will take Atomoxetine (80mg) and Oxybutynin (5mg) before bedtime for 3 nights. Half doses will be given on the first night.

Participants will take Atomoxetine (80mg) and Oxybutynin (5mg) before bedtime for 3 nights. Half doses will be given on the first night.

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
Number of arousals per hour (>=3-sec), % change from baseline

Full Information

First Posted
September 19, 2022
Last Updated
October 16, 2023
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05550246
Brief Title
Identifying Sleep Apnea Patients That Best Respond to Atomoxetine Plus Oxybutynin Therapy
Official Title
Identifying Sleep Apnea Patients That Best Respond to Atomoxetine Plus Oxybutynin Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 5, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Atomoxetine-plus-oxybutynin therapy (AtoOxy) has been shown to substantially reduce obstructive sleep apnea severity (OSA) in about half of patients. Here, the investigators will study which patients respond meaningfully to therapy using pathophysiological traits measured at baseline sleep studies.
Detailed Description
The primary goal of the current study is to test the central hypothesis that therapeutic efficacy of AtoOxy depends on underlying patient pathophysiology. Aim 1 - Advanced analysis of clinical polysomnography will be used to estimate the OSA traits and classify patients as 'predicted responders' or 'predicted nonresponders'. Investigators will prospectively test whether AtoOxy efficacy is greater in predicted responders. Aim 2 - Pooling preliminary and prospective data, investigators will test the hypotheses that the following pathophysiological traits are associated with, and therefore predict, greater efficacy: less-severe upper airway collapsibility (less improvement needed to re-establish airflow), lower loop gain (less severe ventilatory control instability), higher arousal threshold (greater scope for muscle activation without arousal), and greater upper airway muscle compensation (functional muscle reflex apparatus). Aim 3 - Investigators will test the hypothesis that treatment efficacy will be greater in patients with tongue-related upper airway obstruction per previous drug-induced sleep endoscopy results (anterior-posterior collapse patterns).

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
Parallel Assignment
Masking
None (Open Label)
Masking Description
Participants and outcome assessors will be blinded to physiological predicted responder status
Allocation
Non-Randomized
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AtoOxy Predicted Responders
Arm Type
Experimental
Arm Description
Participants will take Atomoxetine (80mg) and Oxybutynin (5mg) before bedtime for 3 nights. Half doses will be given on the first night.
Arm Title
AtoOxy Predicted Nonresponders
Arm Type
Experimental
Arm Description
Participants will take Atomoxetine (80mg) and Oxybutynin (5mg) before bedtime for 3 nights. Half doses will be given on the first night.
Intervention Type
Drug
Intervention Name(s)
Atomoxetine
Intervention Description
Treatment given for 3 nights
Intervention Type
Drug
Intervention Name(s)
Oxybutynin
Intervention Description
Treatment given for 3 nights
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
3 days
Secondary Outcome Measure Information:
Title
Hypoxic Burden
Description
Desaturation area under curve × event frequency
Time Frame
3 days
Title
Arousal Index
Description
Number of arousals per hour (>=3-sec), % change from baseline
Time Frame
3 days

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: Suspected or diagnosed OSA Recent drug induced sleep endoscopy results available (performed as part of routine clinical care). 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, narcolepsy, or parasomnias. Contraindications for atomoxetine and oxybutynin, including: hypersensitivity to atomoxetine or oxybutynin (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 moderate-to-severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline; average of evening and morning measures*) 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 Claustrophobia Pregnancy or nursing n.b. Development of new hypertension that is recognized on the final day of study medications during outcomes collection will not be used as stopping criteria for discontinuing outcomes collection. Participants that are sexually active and able to become pregnant must agree to use birth control for the entire study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Scott A Sands, PhD
Phone
617-278-0911
Email
sasands@bwh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Laura K Gell, PhD
Phone
617-525-9086
Email
lgell@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
02141
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Scott A Sands, PhD
Phone
857-928-0341
Email
sasands@bwh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be available to researchers who provide a methodologically sound proposal. All IPD collected during the study will be available after deidentification.
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.

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Identifying Sleep Apnea Patients That Best Respond to Atomoxetine Plus Oxybutynin Therapy

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