MORPHO: Managing Opioid Related Sleep Apnea With Acetazolamide

Sponsor

University of California, San Diego (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06043830

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

20.1

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with chronic pain who use opioids appear to be at increased risk for breathing issues during sleep, termed sleep disordered breathing (SDB). Treatment of SDB often consists of use of a device during sleep that provides continuous positive airway pressure (CPAP) via a mask interface. However, this device is not effective or tolerated in all individuals. The goal of this study is to examine whether a medication called acetazolamide can improve SDB, as an alternative to CPAP treatment.

The investigators will measure the improvement in SDB, as well as any change in symptoms, during a 1 week treatment with acetazolamide compared with 1 week of placebo (sugar pill). This study will help to provide data for longer term studies of treatment for SDB in patients who use opioids.

Condition or Disease	Intervention/Treatment	Phase
Sleep-Disordered Breathing Obstructive Sleep Apnea Central Sleep Apnea Chronic Pain Opioid Use	Drug: Acetazolamide Other: Placebo	Phase 2

Detailed Description

Patients who use chronic opioids for chronic pain daily for >3 months will be recruited. The investigators will study patients with established sleep disordered breathing (SDB; defined as an apnea-hypopnea index (AHI) >/= 5 events/hr). Patients with a prior diagnosis of SDB can enroll provided they can hold their CPAP treatment for the duration of the study. Persons with chronic lung or kidney disease will be excluded, along with those with heart failure, liver failure, kidney disease, medications affecting potassium levels, recreational opioid use, cancer pain, limited life expectancy, prisoners, pregnant women, psychiatric disease other than controlled mood disorders, and those unable to provide consent or cooperate with research procedures. Potential subjects will discuss the planned research protocol, risks, benefits, and alternatives with the study staff.

Once the individual has given written informed consent, they will be scheduled for a baseline study visit, which will begin in the early evening. Subjects will undergo a comprehensive history and physical exam, questionnaires examining sleep quality, daytime function, pain, and quality of life. The cold pressor test will be administered, which includes submerging the non-dominant hand in a 4 degree Celsius water bath, and reporting the onset of pain and maximal tolerable submersion time.

The subjects will be randomized into two groups: Group A will take acetazolamide 500 mg by mouth nightly for 1 week, followed by placebo (sugar pill) by mouth nightly for 1 week. Group B will take placebo (sugar pill) by mouth nightly for 1 week, followed by acetazolamide 500 mg by mouth nightly for 1 week. There will be a 2 week washout (i.e. no placebo or acetazolamide) between the treatments. The subjects and study staff will be blinded to the treatment that each subject is taking, in order to avoid introducing bias into the results. Study staff will be follow up with a phone call mid-week and will be available by phone if any issues arise.

At the end of each week (acetazolamide and placebo conditions), the subject will return for a follow up visit, during which they will undergo the same assessment tools as the baseline visit. They will then be instrumented for an overnight sleep study, which will include the application of electrodes to the scalp (electroencephalogram), beside the eyes (electro-oculogram), chin and legs (electromyogram). Elastic bands will be applied around the chest and abdomen, a pulse oximeter will be affixed to the finger, and airflow monitors placed just inside the nose and outside the mouth. The subject will then be allowed to sleep until the morning. Upon awakening, they will undergo a computer test of alertness.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Managing Opioid Related Sleep Apnea With Acetazolamide

Anticipated Study Start Date :

Sep 29, 2023

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo followed by acetazolamide Subjects will start with a 1-week PLACEBO regimen Day 1-7: Placebo (matching Acetazolamide) nightly After a 2 week wash-out period, subjects will then cross-over to a 1-week ACETAZOLAMIDE regimen: Day 1-7: Acetazolamide 500 mg nightly	Drug: Acetazolamide Acetazolamide 250 mg 2 capsules by mouth nightly Other: Placebo Sugar capsule manufactured to match encapsulated Acetazolamide 2 capsules by mouth nightly
Experimental: Acetazolamide followed by placebo Subjects will start with a 1-week ACETAZOLAMIDE regimen Day 1-7: Acetazolamide 500 mg nightly After a 2 week wash-out period, subjects will then cross-over to a 1-week PLACEBO regimen: Day 1-7: Placebo (matching Acetazolamide) nightly	Drug: Acetazolamide Acetazolamide 250 mg 2 capsules by mouth nightly Other: Placebo Sugar capsule manufactured to match encapsulated Acetazolamide 2 capsules by mouth nightly

Arm

Intervention/Treatment

Experimental: Placebo followed by acetazolamide

Subjects will start with a 1-week PLACEBO regimen Day 1-7: Placebo (matching Acetazolamide) nightly After a 2 week wash-out period, subjects will then cross-over to a 1-week ACETAZOLAMIDE regimen: Day 1-7: Acetazolamide 500 mg nightly

Drug: Acetazolamide

Acetazolamide 250 mg 2 capsules by mouth nightly

Other: Placebo

Sugar capsule manufactured to match encapsulated Acetazolamide 2 capsules by mouth nightly

Experimental: Acetazolamide followed by placebo

Subjects will start with a 1-week ACETAZOLAMIDE regimen Day 1-7: Acetazolamide 500 mg nightly After a 2 week wash-out period, subjects will then cross-over to a 1-week PLACEBO regimen: Day 1-7: Placebo (matching Acetazolamide) nightly

Drug: Acetazolamide

Acetazolamide 250 mg 2 capsules by mouth nightly

Other: Placebo

Sugar capsule manufactured to match encapsulated Acetazolamide 2 capsules by mouth nightly

Outcome Measures

Primary Outcome Measures

Apnea-hypopnea index [1 week]
The AHI is a measure of sleep apnea severity and is defined as the number of apneas (no breathing for 10+ seconds) and hypopneas (reduced breathing for 10+ seconds associated with a >=3% desaturation or cortical arousal) per hour of sleep.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18+
Chronic pain
Chronic opioid use (daily use for >3 months duration) with >/= 20 oral Morphine Equivalent Dose (MEqD) per day
Apnea-hypopnea index >/= 10 events/hr (hypopnea definition: ≥ 3% desaturation or arousal criteria per American Academy of Sleep Medicine 2012 scoring rules)

Exclusion Criteria:

Use of opioids outside medical supervision (e.g. recreational use)
Unable or unwilling to withhold any ongoing SDB treatment (e.g. CPAP) for the duration of the study
Urgent need to initiate effective SDB therapy
Chronic lung disease (other than well-controlled asthma)
Active cardiac disease including heart failure, chest pain, or heart rhythm problems
Neurological or developmental problems affecting breathing
Major sleep disorders other than sleep apnea
Chronic kidney disease
Cirrhosis of the liver
Active cancer treatment or limited life expectancy
Psychiatric disease other than controlled mood disorders
Use of diuretics, potassium supplementation, or medications that may affect potassium
Allergy to study drug or related compounds including sulfa drugs
Know electrolyte disturbances
Hospitalized in the last 90 days or anticipated hospitalization within 3 months
Alcohol use >2 standard drinks per day
Presence of tracheostomy or artificial airway
Prisoners
Pregnancy or anticipating pregnancy in next 2 months, or nursing
Unable or unwilling to provide informed consent
Unable to follow study protocol