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Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation | Clinical Trials | Clareo Health

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Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation

Clinical Study to Investigate the Effect of Administration of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation

NCT05470465•Food and Drug Administration (FDA)

View on ClinicalTrials.gov

Summary

This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram with an opioid on ventilation. Ventilation will be assessed using a rebreathing methodology. This study will evaluate chronic and acute dosing of paroxetine and escitalopram combined with an opioid as well as chronic and acute dosing of the two drugs without coadministration of an opioid. This study is a 3-period, randomized, placebo-controlled crossover study conducted with 25 healthy participants. Each participant will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, escitalopram/oxycodone) in a randomized order.

Detailed Description

This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram, two selective serotonin reuptake inhibitors (SSRI), with an opioid on hypercapnic ventilation. Hypercapnic ventilation will be assessed under both hyperoxic and hypoxic conditions using the Duffin rebreathing method. This method allows for critical physiological measurements and thresholds to be captured that can then be used to model the effects of drugs when there are dynamic changes in oxygen partial pressure (PO2) and carbon dioxide partial pressure (PCO2), such as during a real-world opioid overdose. SSRIs take approximately 3 weeks to reach maximal therapeutic effect, which correlates with the time required for pre-synaptic inhibitory serotonergic receptors to desensitize. Therefore, drug-effects on ventilation should be evaluated under steady state conditions. This study is randomized, placebo-controlled crossover study which includes three 21-day periods conducted with 25 healthy participants. Participants will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, or escitalopram/oxycodone) in a randomized order. Paroxetine dosing will range from 40-60 mg once daily (QD) and escitalopram dosing will range from 20-30 mg QD. Subjects will receive 10 mg oxycodone on three different days each period. Subjects will undergo 6 days of rebreathing and time-matched pupillary assessments along with 3 separate days of ECG assessments each period. Additionally, blood samples will be collected for determination of plasma concentrations for each study drug on days with rebreathing and ECG assessments.

Eligibility

Age

18 - 50 years

Sex

ALL

Healthy Volunteers

Yes

Inclusion Criteria

•1. Subject signs an Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
•2. Subject is a healthy, non-smoking man or woman, 18 to 50 years of age, inclusive, who has a body mass index of 18.5 to 33.0 kg/m2, inclusive, at Screening.
•3. Subject has normal medical history findings, clinical laboratory results, vital sign measurements, pulse oximetry, 12-lead ECG results, and physical examination findings at screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
•4. Subject must have a negative test result for alcohol and drugs of abuse at screening and check-in days.
•5. Subject must test negative for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) by a rapid antigen test at check-in for all study periods. If a subject's test comes back as invalid, the test can be repeated.
•6. Female subjects must be of non-childbearing potential (confirmed with follicle-stimulating hormone levels \> 40 milli-international unit \[mIU\]/mL) or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before check-in (Day -1) and agree to remain strictly abstinent for the duration of the study and for at least 1month after the last application of study drug; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before check-in (Day -1) until at least 1 month after the end of the study.
•7. Male subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee) from at least 1 month before check-in (Day -1) until at least 1 month after the last dose of study drug.
•8. Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.

Exclusion Criteria

•1. Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug. This includes prescription or nonprescription ophthalmic drugs.
•2. Subject is currently participating in another clinical study of an investigational drug or has been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.
•3. Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, electronic cigarettes) within 6 weeks of Screening. Subjects must refrain from using these throughout the study.
•4. Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, cola), caffeine, grapefruit, or grapefruit juice within 24 h of check-in. Subjects must refrain from ingesting these throughout the study.
•5. Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus \[HIV\], hepatic or renal impairment) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. This includes subjects with any underlying medical conditions that put subjects at increased risk of severe illness from coronavirus disease 2019 (COVID-19) based on the Centers for Disease Control and Prevention (CDC) guidelines.
•6. Subject has any signs or symptoms at screening or check-in of any study periods that are consistent with COVID-19. Per current CDC recommendations this includes subjects with the symptoms cough or shortness of breath or difficulty breathing, or at least two of the following symptoms: fever, chills, repeated shaking with chills, muscle pain, headache, sore throat or new loss of taste/smell. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
•7. Subject has known or suspected allergies or sensitivities to any study drugs.
•8. Subject has clinical laboratory test results (hematology, serum chemistry and urinalysis) at Screening or period check-in that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator. Clinical laboratory results may be repeated once, as needed, for confirming results at Screening and period check-in.
•9. Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
•10. Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
+21 more criteria

Locations (1)

Spaulding Clinical Research

West Bend, Wisconsin, United States

Key Dates

Start Date

September 1, 2022

Primary Completion Date

September 17, 2023

Completion Date

September 17, 2023

Last Updated

May 22, 2025

Enrollment

ACTUAL participants

Conditions

HypercapniaVentilatory Depression

Interventions

Placebo and Oxycodone

DRUG

Paroxetine and Oxycodone

DRUG

Escitalopram and Oxycodone

DRUG

The Effect of Respiratory Challenge on the BOLD Signal

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Hypoxia, BrainHyperoxia+2 more

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COPDCOPD (Chronic Obstructive Pulmonary Disease)+5 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 22, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation

Inclusion Criteria

Exclusion Criteria

The Effect of Respiratory Challenge on the BOLD Signal

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Effects of Walking Apnea at High Lung Volume on Hypoalgesia, Cardiovascular Function and Respiratory Function