Impacts of Opioids on Respiratory Drive During Sleep (OIRD)

Mechanisms of Opioid-induced Respiratory Depression (OIRD) During Sleep

The investigators are studying the impact that opioids have on breathing during sleep in healthy participants and those diagnosed with obstructive sleep apnea.

Study Overview

• Status: Not yet recruiting
• Conditions: Obstructive Sleep Apnea (OSA); Opioids
• Intervention / Treatment: Drug: Morphine p.o.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Nicole Calianese; Phone Number: 617-732-8977; Email: ncalianese@mgb.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
      • Contact: Nicole Calianese; Phone Number: 617-732-8977; Email: ncalianese@mgb.org
      • Principal Investigator: Danny J Eckert, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy controls: Apnea Hypopnea Index (AHI) < 5 events/hr on in-laboratory PSG within 3 months of enrollment
• OSA group: AHI > 10 events/hr on in-laboratory PSG within 3 months of enrollment; treated or untreated.

Exclusion Criteria:

• Sleep disordered breathing or respiratory disorders (other than OSA in the OSA group), such as central sleep apnea (>50% of respiratory events scored as central), 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 index > 20/hr), narcolepsy, or parasomnias.
• Any unstable major medical condition.
• Medications expected to stimulate or depress respiration (including other opioids taken at home, barbiturates, benzodiazepines, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• History of allergy to lidocaine or oxymetazoline.
• Contraindications for morphine, including:
• allergy to morphine or opioids
• chronic obstructive pulmonary disease, asthma, or other significant respiratory disorders
• kidney or liver dysfunction, as this can affect the metabolism and excretion of morphine, leading to increased risk of toxicity.
• women who are pregnant or breastfeeding will be excluded due to potential risks to the fetus or infant.
• history of substance abuse, particularly opioid abuse, will be excluded to prevent potential misuse or relapse.
• current use of central nervous system depressants.
• individuals with gastrointestinal obstruction. Constipation is not an exclusion criterion because morphine is only administered for one night.
• recent head injury, brain tumors, or other conditions leading to increased intracranial pressure.
• unstable heart disease, particularly those with risk factors for or a history of heart rhythm disorders.
• epilepsy or a history of seizures, as morphine can lower the seizure threshold.
• severe psychiatric conditions, particularly those with a history of psychosis, as opioids can exacerbate these conditions.
• medications that interact with morphine, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), Monoamine oxidase inhibitors (MAOIs), and the atypical antidepressants buproprion and trazodone.
• untreated or unstable endocrine disorders like adrenal insufficiency or thyroid dysfunction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo will be given on the sleep study night.
Active Comparator: Morphine	Drug: Morphine p.o.; Morphine 50mg PO will be given on sleep study night.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in ventilation (L) per minute during stable sleep with morphine versus placebo.	The primary outcome, determining the change in ventilation in liters per minute, will be analyzed on both subpopulations (controls and people with obstructive sleep apnea) using generalized linear mixed models with treatment, period and sequence as fixed effects and a random effect of participant nested within sequence.	From enrollment to the end of treatment at 6 weeks.

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Danny J Eckert, PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 3, 2025

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 2024P002115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD at this time.

Drug and device information, study documents

• 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