Acetazolamide in Central Sleep Apnea Patients Using Medication for Opioid Use Disorder

Sanjay R Patel

Status and phase: Enrolling; Phase 2

Conditions: Central Sleep Apnea Comorbid With Opioid Use

Treatments: Drug: Acetazolamide; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06521476

STUDY23100016

R01DA059465 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

Acetazolamide

Experimental group

Description:

All participants in this group will receive one acetazolamide 250 mg pill in the evening for 7 days.

Treatment:

Drug: Acetazolamide

Placebo

Placebo Comparator group

Description:

All participants in this group will receive one matching placebo pill in the evening for 7 days.

Treatment:

Drug: Placebo