Oxygen + Acetazolamide for Sleep Apnea (SDB Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: VA Office of Research and Development
No Placebo Group
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?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.
What safety data exists for the use of acetazolamide in treating sleep apnea?Acetazolamide has been associated with potential safety concerns, including the risk of anaphylactic shock in individuals with sulfonamide allergies, as highlighted by a fatal case. Additionally, metabolic acidosis was observed in some patients treated for sleep apnea. Careful consideration of patient history regarding sulfonamide allergies is advised before prescribing acetazolamide.12678
Is the drug Acetazolamide promising for treating sleep apnea?Yes, Acetazolamide shows promise for treating sleep apnea. Studies indicate it can reduce the number of apnea episodes and improve sleep quality in many patients. It also helps with symptoms like daytime sleepiness and snoring, especially in mild cases of obstructive sleep apnea.347911
What data supports the idea that Oxygen + Acetazolamide for Sleep Apnea is an effective treatment?The available research shows that acetazolamide, a drug, can help reduce the number of apnea episodes and improve sleep quality in some patients with sleep apnea. For example, in one study, 14 out of 20 patients experienced fewer apnea episodes and better sleep after using acetazolamide. Another study found that acetazolamide reduced the average number of apnea episodes from 25 to 18 per hour in patients. Additionally, it improved the time patients spent with low oxygen levels during sleep. However, it's important to note that not all patients responded to the drug, and it may be more effective in mild cases of sleep apnea. Compared to other treatments like CPAP, which some patients find difficult to use, acetazolamide offers an alternative, especially for those traveling to high altitudes where sleep apnea can worsen.4571011
Do I have to stop taking my current medications for the trial?The trial does not specify if you need to stop taking your current medications, but it does require that you are on prescription opioids. Patients on tramadol and suboxone/buprenorphine are excluded.
Eligibility Criteria
This trial is for veterans aged 18-89 who are on prescription opioids and may have sleep issues like apnea due to their medication. It's not open to those with severe untreated mental or physical health conditions, recent strokes or heart problems, pregnant women, very high BMI (>40), or anyone unable to consent.Inclusion Criteria
I am a veteran prescribed opioids.
Exclusion Criteria
I have ongoing chest pain or discomfort.
I do not have severe lung, brain, liver, or kidney diseases.
I am currently taking tramadol and suboxone/buprenorphine.
I have ongoing seizures that aren't controlled.
I do not have any untreated heart conditions, including recent heart attacks or surgeries.
I have heart failure with specific breathing patterns.
I have schizophrenia that has not been treated.
I have had a stroke recently.
I have had a traumatic brain injury.
I have a serious sleep disorder like narcolepsy.
I have hypothyroidism that has not been treated.
My BMI is over 40.
Participant Groups
The study tests if oxygen (hyperoxia) and a drug called acetazolamide can help reduce irregular breathing and eliminate sleep apnea in people taking chronic opioid medications. It also looks at how these treatments affect life quality, sleep, and pain levels.
2Treatment groups
Experimental Treatment
Group I: HyperoxiaExperimental Treatment1 Intervention
Determine the effect of sustained hyperoxia overnight vs room air overnight on ventilatory control during sleep, including the apneic threshold, carbon-dioxide reserve and chemosensitivity measured via pressure support ventilation (PSV) during non-rapid eye movement sleep (NREM) sleep.
Group II: Acetazolamide (ACZ)Experimental Treatment1 Intervention
Determine the effect of acetazolamide on cerebrovascular responsiveness to CO2 during wake and sleep. Participants will receive oral ACZ therapy for 6 days, While on the medication following studies will be performed - experimental night study, experimental day study, polysomnography night study (PSG).
Acetazolamide is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Diamox for:
- Glaucoma
- Epilepsy
- Edema
- Altitude sickness
🇪🇺 Approved in European Union as Diamox for:
- Glaucoma
- Epilepsy
- Edema
🇨🇦 Approved in Canada as Diamox for:
- Glaucoma
- Epilepsy
- Edema
- Altitude sickness
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
John D Dingell VAMCDetroit, MI
John D. Dingell VA Medical Center, Detroit, MIDetroit, MI
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Who is running the clinical trial?
VA Office of Research and DevelopmentLead Sponsor
John D. Dingell VA Medical CenterCollaborator
References
Short-term dose response characteristics of acetazolamide in man. [2019]Nine patients with ocular hypertension each randomly received on separate days 0, 63, 125, 250, and 500 mg of acetazolamide (Diamox). In a double masked manner, acetazolamide plasma levels and intraocular pressure were monitored for seven hours following administration. Plasma levels increased linearly with dose, reaching 30 microgram/ml with the 500-mg dose. Maximum plasma levels occurred at one hour, and the minimum IOP was at two hours. The maximum IOP effect was a 30% to 35% fall. The IOP response was related to dose and plasma level, up to a 63-mg dose, which produced an average fall of 8.2 mm Hg. Little further average effect was documented at higher doses or plasma levels. The duration of response was slightly prolonged by 250 mg, but 500 mg showed no greater response. Thus, a 63-mg dose or a plasma level of 4 to 5 microgram/ml was as effective in lowering IOP as higher doses that produced plasma levels of 10 microgram/ml or more.
Inadvertent substitution of acetohexamide for acetozolamide. [2019]In three cases acetohexamide (Dymelor), an oral hypoglycemic agent, was mistakenly given to patients instead of acetazolamide (Diamox), which had been prescribed for their glaucoma. A number of similarities, including the fact that both medications are 250-mg white tablets, with similar generic and brand names which are generically repackaged medications juxtaposed on the pharmacist's shelf, predispose to the inadvertent substitution of one medication for the other. In one instance a systemic hypoglycemic reaction resulting in head trauma and confusion ended in an emegency hospital admission following the substitution of acetohexamide for acetazolamide.
Acetazolamide and high altitude diseases. [2013]Acetazolamide is a useful prophylactic for acute mountain sickness causing marked reduction in headache, nausea, vomiting, weakness, etc. Improvements correlate with increased arterial oxygen concentrations, reduction in proteinuria and peripheral oedema and other objective measures of acute mountain sickness. Evidence that Acetazolamide is beneficial for pulmonary oedema or cerebral oedema is scanty because of the lower frequency of these severe forms of mountain sickness. Dexamethasone, used prophylactically, also reduces the symptoms of acute mountain sickness partly due to its euphoric effect. Use of Acetazolamide as a treatment for established acute mountain sickness has been investigated. Large doses of Acetazolamide increase arterial oxygen levels over a few hours and this leads to a reduction of symptoms but data is limited and faster acting carbonic anhydrides inhibitors such as Methazolamide may be preferable in an emergency situation. There is no comparison of the effectiveness of Acetazolamide with other drugs used for treating acute mountain sickness such as steroids and calcium channel blocking drugs. Also, there is no data on drug combinations which could have additive effects and thereby be more beneficial than individual drugs.
Effects of acetazolamide in patients with the sleep apnoea syndrome. [2019]There is as yet no convincing evidence that acetazolamide, a carbonic anhydrase inhibitor, is effective in obstructive sleep apnoea. A study was therefore designed to examine the effect of acetazolamide (250 mg/day) on sleep events and ventilatory control during wakefulness in nine patients with the sleep apnoea syndrome. In eight of the nine patients the apnoea index and the total duration of apnoea were reduced by acetazolamide, and the mean (SEM) apnoea index of all patients changed from 25.0 (6.7) to 18.1 (5.8) episodes an hour. Furthermore, the total time of arterial oxygen desaturation (SaO2)--more than 4% depression in SaO2 from the baseline sleeping level--divided by total sleep time was also significantly decreased and its mean (SEM) value improved from 24.1 (7.9) to 13.6 (4.8)% of total sleep time. Five of the seven patients with varying degrees of daytime hypersomnolence had their symptoms obviously improved. There was no patient whose predominant type of apnoea was converted from the obstructive to the central type, or vice versa. In the studies of wakefulness, metabolic acidosis, an increase of arterial oxygen tension (PaO2) and a decrease of arterial carbon dioxide tension (PaCO2) were observed. The slopes of the occlusion pressure response and the ventilatory response to carbon dioxide increased, and the carbon dioxide ventilatory response line shifted to the left. It is suggested that acetazolamide cannot remove apnoea completely but has a beneficial effect in mild cases of obstructive sleep apnoea through an augmentation of central (CO2, H+) drive and a stabilising effect on ventilatory control.
Central sleep apnea. Improvement with acetazolamide therapy. [2013]Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5 +/- 0.54 mm Hg. This may be important in mediating the observed decrease in apneas.
Effectiveness of generic acetazolamide. [2019]Comparisons were made between the ocular hypotensive effects and blood levels achieved with the single-dose administration of either generic acetazolamide or brand-name acetazolamide (Diamox). The relative cost of the two products was surveyed. The effect of food on the absorption of acetazolamide was also evaluated. The generic and brand-name acetazolamide were equivalent in their effects on intraocular pressure. Comparable blood levels of acetazolamide were obtained with the two products. The cost of generic acetazolamide was 37% less than brand-name acetazolamide, when available. Food intake did not appear to influence the absorption of acetazolamide.
Effects of acetazolamide on the sleep apnea syndrome and its therapeutic mechanism. [2019]Twenty male patients with sleep apnea syndrome were treated with acetazolamide (AZM), a carbonic anhydrase inhibitor. In 14 of the patient a significant decrease was found in the number of apnea, apnea index and % apnea time (percentage of time spent with apnea to the total sleep time) with improvement in sleep structure, clinical symptoms, such as insomnia, daytime excessive sleepiness and snoring. A significant decrease was also observed in arterial blood pH and HCO-3 in the 14 improved patients. On the other hand, no improvement occurred in the parameters of sleep apnea and sleep with AZM in the remaining six patients. Moreover, metabolic acidosis and an improvement in arterial blood gases did not occur with AZM in the six patients.
[Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma]. [2017]A woman aged 66 was prescribed acetazolamide (Diamox) in the outpatient clinic because of glaucoma. She went into irreversible anaphylactic shock with massive pulmonary oedema, probably due to a cross reaction in sulphonamide allergy. Before prescribing acetazolamide, the physician should inquire about sulphonamide allergy because of the related chemical structure of the substances. Such an allergy should be regarded as a contraindication.
Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. [2022]Acetazolamide is a mild diuretic and a respiratory stimulant. It is used to treat periodic breathing at high altitude.
Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial. [2017]Many patients with obstructive sleep apnea syndrome (OSA) are unable or unwilling to use continuous positive airway pressure (CPAP) therapy when traveling to the mountains for work or recreation even though they risk pronounced hypoxemia and exacerbation of sleep apnea. Because the treatment of OSA at altitude has not been established, we tested the hypothesis that acetazolamide improves hypoxemia, sleep, and breathing disturbances in otherwise untreated patients with OSA at altitude.
The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. [2018]Acetazolamide has been investigated for treating sleep apnea in newcomers ascending to high altitude. This study aimed to assess the effect of acetazolamide on sleep apnea at high altitude, determine the optimal therapeutic dose, and compare its effectiveness in healthy trekkers and obstructive sleep apnea (OSA) patients.