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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

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

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.

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

NCT ID

NCT05550246

First Posted

September 19, 2022

Last Updated

October 16, 2023

Sponsor

Brigham and Women's Hospital

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

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

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

sasands@bwh.harvard.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Laura K Gell, PhD

Phone

617-525-9086

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

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.

Learn more about this trial

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

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