Oxygen + Finasteride + Acetazolamide for Sleep Apnea in Elderly

Recruiting at 1 trial location

Overseen By Ruchi Rastogi, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Narcotics, Antidepressants, Antipsychotics, others

Disqualifiers: Severe sleep apnea, Cardiac disease, Stroke, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how oxygen, finasteride, and acetazolamide (a diuretic medication) can reduce sleep apnea in elderly Veterans. The goal is to determine if these treatments can stabilize breathing during sleep and improve overall health. The trial invites individuals aged 60 and older with mild to moderate sleep apnea, with a focus on men for the finasteride segment. Participants will be divided into groups to assess the different effects of each treatment. This research could lead to improved sleep apnea treatments for the elderly. As a Phase 4 trial, the treatments have already received FDA approval and demonstrated effectiveness, and this research aims to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including study drugs, narcotics, antidepressants, anti-psychotic agents, and other medications that affect the central nervous system. If you are on any of these, you may need to stop them to participate.

What is the safety track record for these treatments?

In a previous study, acetazolamide lowered blood pressure and alleviated breathing problems during sleep in individuals with obstructive sleep apnea. It was safe for use up to 90 days, with doses ranging from 36 to 1000 mg per day. Another study demonstrated that acetazolamide improved low oxygen levels at night and supported better breathing during sleep.

Research shows that oxygen therapy can raise oxygen levels in people with sleep apnea. However, some studies suggest it might also prolong breathing pauses during sleep. While potentially helpful, the results on its safety and effectiveness are mixed.

A safety review of finasteride, particularly at the 1 mg dose, examined reports of side effects and existing studies. Although typically used for other conditions, it may increase the risk of obstructive sleep apnea, necessitating careful monitoring.

Overall, these treatments have shown some benefits but also carry potential risks. Consulting a healthcare provider is crucial to weigh the benefits and possible side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for sleep apnea in the elderly because they explore new ways to address breathing issues during sleep. Acetazolamide is being tested for its potential to enhance how blood vessels respond to carbon dioxide, potentially improving breathing regulation. Hyperoxia, or increased oxygen levels, aims to stabilize breathing patterns by altering the body's response to carbon dioxide overnight. Finasteride, typically known for treating enlarged prostate, is being tested for its influence on sleep-disordered breathing by possibly affecting hormone levels that impact airway stability. These approaches offer fresh angles compared to standard treatments like CPAP machines or positional therapy by targeting the underlying physiological mechanisms.

What evidence suggests that this trial's treatments could be effective for sleep apnea?

This trial will evaluate the effects of acetazolamide, hyperoxia (oxygen therapy), and finasteride on sleep apnea in elderly participants. Research has shown that acetazolamide, one of the treatments in this trial, can help with sleep apnea by reducing breathing interruptions and improving oxygen levels during sleep. It helps maintain steady breathing throughout the night.

Hyperoxia, another treatment option in this trial, can boost oxygen levels in the blood. However, studies have shown mixed results regarding its overall effect on sleep apnea. Some research indicates it improves oxygen levels but doesn't always reduce the duration of breathing disruptions.

Finasteride, also under study in this trial, has some evidence suggesting it might help stabilize breathing during certain sleep stages, like deep sleep (NREM). However, other studies suggest it might increase the risk of obstructive sleep apnea, making its effects complex and not fully understood.

Overall, acetazolamide appears to be the most promising option for helping with sleep apnea based on current research. ^{1 5 6 7 8}

Who Is on the Research Team?

Susmita Chowdhuri, MD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Are You a Good Fit for This Trial?

This trial is for elderly adults aged 60 and older with mild to moderate sleep apnea (AHI of 5-20/hr). It's specifically for men when testing finasteride. People with severe sleep apnea, prostate cancer, heart disease, schizophrenia, untreated thyroid issues, seizure disorders, kidney or liver problems can't join. Also excluded are those on certain medications or who use alcohol or tobacco.

Inclusion Criteria

I am an elderly man eligible for the finasteride study.

I am 60 or older with mild to moderate sleep apnea.

I am an elderly man eligible for the finasteride study.

Exclusion Criteria

I have not received treatment for low thyroid hormone levels.

I have a seizure disorder.

I have kidney or liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive interventions with sustained hyperoxia, finasteride, and acetazolamide to study their effects on sleep apnea

4 weeks

Multiple visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• Finasteride
• Hyperoxia/oxygen

Trial Overview

The study tests if oxygen therapy (hyperoxia), the drug finasteride, and acetazolamide can help reduce unstable breathing in elderly people with sleep apnea. The goal is to find new treatments that improve their quality of life by targeting different mechanisms causing the condition.

How Is the Trial Designed?

Group I: Hyperoxia Experimental Treatment 1 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: Finasteride Experimental Treatment 1 Intervention

Determine the effect of oral finasteride therapy vs placebo for 1 month on SDB and the AT and chemosensitivity during NREM sleep.

Group III: Acetazolamide (ACZ) Experimental Treatment 1 Intervention

Determine the effect of acetazolamide on cerebrovascular responsiveness to CO2 during wake and sleep. Participants will receive oral ACZ therapy for 7 days prior to the experimental night, on the night of the study and the subsequent night when polysomnography (PSG) will be performed.

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

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a study of nine patients with obstructive sleep apnoea, acetazolamide (250 mg/day) significantly reduced the apnoea index from 25.0 to 18.1 episodes per hour and decreased the total time of arterial oxygen desaturation during sleep.

Acetazolamide appears to improve symptoms of daytime hypersomnolence in some patients and enhances ventilatory control by increasing the body's response to carbon dioxide, suggesting it may be beneficial for mild cases of obstructive sleep apnoea, although it does not completely eliminate apnoea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide in patients with the sleep apnoea syndrome. Tojima, H., Kunitomo, F., Kimura, H., et al.[2019]

Finasteride effectively reduces levels of 5 alpha-dihydrotestosterone (5 alpha-DHT) by about 80%, leading to a significant reduction in prostate size (20-25%) and improvement in prostatic symptoms (30%) in men with benign prostatic hyperplasia (BPH), particularly in those with larger prostate glands (over 40 ml).

While finasteride is generally well tolerated, with a low incidence of side effects, it may cause sexual side effects in about 3-4% of patients, including impotence and decreased ejaculatory volume.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A risk-benefit assessment of treatment with finasteride in benign prostatic hyperplasia. Ekman, P.[2018]

In a study of 20 male patients with sleep apnea, 14 showed significant improvements in apnea frequency, sleep structure, and related symptoms after treatment with acetazolamide (AZM), a carbonic anhydrase inhibitor.

The treatment led to a decrease in arterial blood pH and bicarbonate levels in the improved patients, indicating a potential mechanism of action related to metabolic changes, while the remaining 6 patients did not experience any benefits from AZM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide on the sleep apnea syndrome and its therapeutic mechanism. Sakamoto, T., Nakazawa, Y., Hashizume, Y., et al.[2019]

In a study involving 45 patients with obstructive sleep apnea (OSA), acetazolamide significantly improved oxygen levels and reduced breathing disturbances at high altitudes compared to a placebo, indicating its potential as an alternative treatment when CPAP is not used.

Acetazolamide not only enhanced nocturnal oxygen saturation and reduced apnea/hypopnea indices but also improved sleep quality and prevented high blood pressure during altitude exposure, suggesting it stimulates ventilation effectively in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial. Nussbaumer-Ochsner, Y., Latshang, TD., Ulrich, S., et al.[2017]

Acetazolamide (AZT) significantly improved sleep apnea symptoms in patients with high loop gain sleep apnea (HLGSA) both acutely and over a 3-month period, showing a notable reduction in the apnea hypopnea index (AHI) and breathing-related arousal index when combined with positive airway pressure (PAP) therapy.

The study involved 231 participants, with a strong predictor for treatment response being the non-rapid eye movement (NREM) AHI, indicating that AZT is a well-tolerated and effective option for managing HLGSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. Ni, YN., Holzer, RC., Thomas, RJ.[2023]

Acetazolamide significantly improves sleep apnea at high altitudes by reducing the Apnea-Hypopnea Index (AHI) and increasing nocturnal oxygenation, particularly in healthy trekkers compared to those with obstructive sleep apnea (OSA).

A daily dose of 250 mg of acetazolamide may be as effective as higher doses for healthy individuals, suggesting a potential optimal therapeutic dose for treating sleep apnea in high-altitude conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. Liu, HM., Chiang, IJ., Kuo, KN., et al.[2018]

In a study involving 14 patients with chronic obstructive pulmonary disease (COPD), acetazolamide significantly improved blood oxygen levels (paO2) in the short term, rising from 49 mm Hg to 58 mm Hg, while placebo led to a decrease.

Long-term treatment with acetazolamide maintained stable oxygen levels in patients, preventing a significant drop in paO2, and was found to be safe with no severe side effects or metabolic acidosis reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acetazolamide in hypercapnic chronic obstructive lung disease--a renaissance?]. Häcki, MA., Waldeck, G., Brändli, O.[2016]

Finasteride effectively reduces levels of the hormone DHT, leading to a 20% reduction in prostate size and a 50% decrease in PSA levels, providing moderate improvement in urinary flow and symptoms for patients with benign prostatic hypertrophy (BPH).

While Finasteride is generally safe for treating BPH, it can cause side effects such as impotence in 3% of patients and decreased ejaculatory volume, but it is also effective in preventing bleeding associated with BPH and can help stop male baldness in younger men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finasteride in the treatment of benign prostatic hypertrophy: an update. New indications for finasteride therapy. Ekman, P.[2019]

A 30-year-old man experienced significant muscle aches and elevated creatine kinase levels after taking finasteride for 10 years, indicating a potential link between the medication and muscle-related side effects.

The patient's symptoms and elevated creatine kinase levels returned to normal within three weeks after stopping finasteride, suggesting that myalgia and hyperCKemia can be reversible adverse reactions to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finasteride-induced myalgia and HyperCKemia. Al-Harbi, TM., Kagan, J., Tarnopolsky, MA.[2015]

Finasteride effectively reduces prostate gland enlargement in patients with benign prostatic hyperplasia, with a recommended dosage of 5 mg once daily, showing rapid and predictable results.

The drug has a low incidence of adverse effects, primarily causing sexual side effects like impotence and decreased libido, and has been safely administered at much higher doses (up to 80 mg/day) without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finasteride: the first 5 alpha-reductase inhibitor. Sudduth, SL., Koronkowski, MJ.[2013]

Finasteride use is significantly associated with an increased reporting of obstructive sleep apnea (OSA), with a reporting odds ratio of 5.65, indicating a strong potential safety signal for this condition among users.

The study also found that finasteride is linked to a higher than expected incidence of insomnia, with a reporting odds ratio of 1.93, suggesting that patients experiencing post-finasteride syndrome symptoms should be evaluated for sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finasteride Use Is Associated with Higher Odds of Obstructive Sleep Apnea: Results from the US Food and Drug Administration Adverse Events Reporting System. Gupta, MA., Vujcic, B., Gupta, AK.[2021]

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