Oxygen + Finasteride + Acetazolamide for Sleep Apnea in Elderly

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Susmita Chowdhuri, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing three treatments—oxygen, finasteride, and acetazolamide—to help elderly Veterans with sleep apnea. These treatments aim to make breathing more stable during sleep by providing extra oxygen, altering hormone levels, and changing how the body handles carbon dioxide. The goal is to find easier and more effective ways to treat sleep apnea in this group.

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 evidence supports the effectiveness of the drug acetazolamide for treating sleep apnea in elderly patients?

Research shows that acetazolamide can reduce the number of apnea episodes and improve oxygen levels during sleep in patients with sleep apnea, especially at high altitudes. It has been found to improve symptoms like daytime sleepiness and snoring in some patients, although it may not be effective for everyone. ^{1 2 3 4 5}

Is the combination of oxygen, finasteride, and acetazolamide safe for treating sleep apnea in elderly patients?

Finasteride, one of the components, has been associated with side effects such as erectile dysfunction, fatigue, cognitive impairment, sleep disturbances, and a potential link to obstructive sleep apnea. It is generally well-tolerated but can cause impotence and decreased libido in some patients. There is no specific safety data available for the combination of oxygen, finasteride, and acetazolamide for sleep apnea. ^{6 7 8 9 10}

How does the drug combination of acetazolamide, finasteride, and oxygen therapy differ from other treatments for sleep apnea?

This treatment is unique because it combines acetazolamide, which helps improve breathing by increasing the body's response to carbon dioxide, with finasteride and oxygen therapy, potentially offering a novel approach for managing sleep apnea in elderly patients who may not tolerate standard treatments like CPAP (continuous positive airway pressure). ^{1 2 3 5 11}

Research Team

Susmita Chowdhuri, MD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Eligibility Criteria

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 60 or older with mild to moderate sleep apnea.

Exclusion Criteria

I have not received treatment for low thyroid hormone levels.

I have a seizure disorder.

I have kidney or liver problems.

Trial Timeline

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

Treatment Details

Interventions

• Acetazolamide (Other)
• Finasteride (Other)
• Hyperoxia/oxygen (Other)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Findings from Research

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 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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide in patients with the sleep apnoea syndrome. [2019]

3. United States 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. [2017]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide on the sleep apnea syndrome and its therapeutic mechanism. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Finasteride: the first 5 alpha-reductase inhibitor. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Finasteride-induced myalgia and HyperCKemia. [2015]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

11. Switzerland pubmed.ncbi.nlm.nih.gov

[Acetazolamide in hypercapnic chronic obstructive lung disease--a renaissance?]. [2016]