Clinical trial NCT06521476: Acetazolamide in Central Sleep Apnea Patients Using Medication for Opioid Use Disorder
Official title: Impact of Acetazolamide on Central Sleep Apnea Patients Receiving Medication for Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Central Sleep Apnea Comorbid With Opioid Use
Keywords: Acetazolamide
Opioid Use Disorder
Medication for opioid use disorder (MOUD)
Methadone
Buprenorphine
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2024-07-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in 1:1 fashion to one of two parallel arms (active drug versus placebo).
Primary purpose: TREATMENT

Brief summary: Patients with opioid use disorder treated with either methadone or buprenorphine are at risk of developing central sleep apnea (CSA) from these medications. Investigators will conduct a mechanistic trial using acetazolamide, a medicine known to improve CSA in other settings, to determine if acetazolamide can improve CSA due to medication for opioid use disorder and whether this leads to physiologic changes that might lead to reduced drug craving. Patients treated with medication for opioid use disorder and who have central sleep apnea will be randomized to treatment with acetazolamide or matching placebo for 7 days. At the end of the 7 days, they will undergo an overnight sleep study to assess the impact on breathing during sleep as well as sleep quality. In addition, measures of sympathetic tone, anxiety, arousal, cognition, and drug craving will be measured to determine if treatment of CSA with acetazolamide can produce physiologic changes that might contribute to improved health.

Detailed description: Medications used to treat opioid use disorder (MOUD) such as methadone and buprenorphine have been found to cause central sleep apnea (CSA), but the clinical ramifications are unclear. It has been hypothesized that the sleep fragmentation and intermittent hypoxemia caused by CSA from MOUD may lead to sympathetic activation, nocturnal arousal, increased anxiety, and cognitive impairment that may in turn increase drug craving and drug relapse. This mechanistic study will evaluate the potential adverse effect of CSA in patients on MOUD by evaluating the impact of acetazolamide to improve CSA and thereby lead to downstream physiologic changes in measures of sleep quality, sympathetic tone, nocturnal arousal, anxiety, cognitive functioning, and drug craving.

Eligible individuals will undergo an overnight research visit including overnight polysomnography, assessments of autonomic tone, sleep quality, nocturnal arousal, emotional distress, cognitive testing, and drug craving. Individuals with opioid-induced CSA will be randomized into a parallel-arm trial of acetazolamide vs. placebo with overnight research visit for outcome assessment at 7 days.

Eligibility criteria: Inclusion Criteria:

* Patients on Medication for Opioid Use Disorder (MOUD) with central sleep apnea.

Exclusion Criteria:

* Sleep-related Hypoventilation.
* Other causes of Central Sleep Apnea besides Opioid Use.
* Pregnancy.
* Contraindications for Acetazolamide.

Primary outcomes:
measure: Central Apnea Index (CAI)
timeFrame: 7 days
Secondary outcomes:
measure: Low frequency / high-frequency ratio (LF/HF ratio)
timeFrame: 7 days
measure: Apnea Hypopnea Index (AHI)
timeFrame: 7 days
Other outcomes:
measure: Overnight urinary norepinephrine levels
timeFrame: 7 days
measure: Pre-ejection period
timeFrame: 7 days
measure: Pre-sleep Arousal Scale (PSAS) score
timeFrame: 7 days
measure: Arousal Index
timeFrame: 7 days
measure: Generalized Anxiety Disorder 7 (GAD-7) score
timeFrame: 7 days
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance score
timeFrame: 7 days
measure: Opioid cue-induced drug craving
timeFrame: 7 days
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Sanjay R Patel, MD
role: PRINCIPAL_INVESTIGATOR
References: