Sleep Disordered Breathing With Opioid Use

Opioid Use Clinical Trial

— SDB  

Official title:

Targeting Chemoreceptor Control of Breathing During Sleep to Mitigate Opioid-Associated Sleep Disordered Breathing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05589753
• Other study ID #: PULM-003-18F
• Secondary ID: 1904002203
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: VA Office of Research and Development
• Contact: Ruchi Rastogi, MSc
• Phone: (313) 576-1000
• Email: ruchi.rastogi[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is an increased risk for sleep disordered breathing (SDB), sleep-related hypoventilation and irregular breathing in individuals on chronic prescription opioid medications. Almost 30% of a veteran sleep clinic population had opioid-associated central sleep apnea (CSA). The proposal aims to identity whether oxygen and acetazolamide can be effective in reducing unstable breathing and eliminating sleep apnea in chronic opioid use via different mechanisms. We will study additional clinical parameters like quality of life, sleep and pain in patients with and without opioid use. This proposal will enhance the investigators' understanding of the pathways that contribute to the development of sleep apnea with opioid use. The investigators expect that the results obtained from this study will positively impact the health of Veterans by identifying new treatment modalities for sleep apnea.

Description:

In a national sample of Veterans, SDB was a significant risk factor for opioid-related toxicity and overdose; and the presence of CSA combined with chronic prescription opioid use compounded the mortality risk. There are only limited and partially effective therapies for this sleep disorder and the exact mechanisms by which opioids produce SDB in adults remain unclear, and varied and conflicting ventilatory control mechanisms have been suggested. This proposal will investigate whether alternative therapies can be developed by modulating specific physiologic mechanisms of ventilatory control. Specifically, the investigators will study effects of chronic oral prescription opioids on chemoresponsiveness and cerebrovascular responsiveness (CVR) (Aim 1); and whether interventions with sustained hyperoxia (Aim 2) and acetazolamide (Aim 3) will reduce the apneic threshold (AT) to alleviate breathing instability and SDB in chronic prescription opioid-associated SDB. The proposed aims will also allow us to delineate key mechanisms of breathing instability with opioid and without opioid use. The information garnered from the proposed experiments will drive development of novel personalized therapies to reduce SDB associated with chronic opioids in Veterans and, ultimately, will positively impact their long-term health and well-being.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• Veterans, age 18-89 years

• Veterans with prescription opioids

Exclusion Criteria:

• Patients with BMI>40kg/m2 will be excluded to avoid the effects of morbid obesity on pulmonary mechanics and ventilatory control

• Patients with history of unresolved/untreated cardiac disease, including recent myocardial infarction, recent bypass surgery, untreated atrial and ventricular tachy-bradycardias

• Congestive heart failure with Cheyne-Stokes respiration (CSR)

• Current unstable angina

• Recent stroke

• Untreated schizophrenia

• Untreated hypothyroidism

• Unresolved seizure disorder

• Severe respiratory, neurological, liver and renal diseases

• Unstable psychiatric disorders/untreated PTSD

• Traumatic brain injury

• Pregnant women

• Significant sleep disorder such as narcolepsy, parasomnias disorder

• Failure to give informed consent

• Patients on tramadol and suboxone/buprenorphine

Related Conditions & MeSH terms

• Opioid Use
• Respiratory Aspiration
• Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Disordered Breathing

Intervention

Other:
• Hyperoxia
The ventilatory effects of brief hyperoxia will be assessed by analyzing control breaths on room air immediately preceding the hyperoxic exposure, and comparing with the primary end-point, nadir minute ventilation breath, immediately following the brief hyperoxic exposure.

Drug:
• Acetazolamide
Participants with sleep apnea will ingest capsules containing either placebo or acetazolamide 500 mg twice a day for 6 days. On the final 4 consecutive nights while still on ACZ, the investigators will perform i) physiology tests and ii) in-lab follow-up PSG.

Locations

Country	Name	City	State
United States	John D. Dingell VA Medical Center, Detroit, MI	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	John D. Dingell VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apneic threshold- a measure of breathing instability	Measures of breathing instability including: Apneic threshold: this is the end-tidal Co2 at which a central apnea closes to a hypopnea is produced.	2 days to 30 days
Primary	Cerebrovascular responsiveness to carbon-dioxide	Cerebrovascular response to different levels of CO2: this is a measure of the response of the cerebral blood flow to changes in carbon dioxide levels and is used as a measure of ventilatory control of breathing	7 days
Primary	Ventilatory responsiveness	Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.	2 days to 30 days
Primary	Carbon -dioxide reserve	This is a derived measure. This is calculated as the difference between the apneic threshold PETCO2 (given above) and the control PETCO2.	2 days to 30 days
Secondary	Apnea hypopnea index	Apnea hypopnea index- is a measure of severity of sleep apnea - this is calculated as the total number of apneas and hypopneas recorded during a sleep study divided by the total sleep time during the sleep study.	2 days to 30 days