Atorvastatin + CPAP for Sleep Apnea

Overseen By Sanja Jelic, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must not be taking: All medications

Disqualifiers: Coronary artery disease, heart failure, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if atorvastatin, a medication typically used to lower cholesterol, can reduce inflammation in individuals with obstructive sleep apnea (OSA) who use a CPAP machine (Continuous Positive Airway Pressure Therapy). Researchers seek to discover whether atorvastatin can aid in reducing inflammation and blood clot risks by improving how blood vessels manage cholesterol. Participants will be divided into two groups: one taking atorvastatin and the other taking a placebo (a pill with no active medication). This trial suits adults recently diagnosed with OSA who have not previously used CPAP treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that participants do not regularly use any medications, so you would need to stop taking your current medications to join.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that atorvastatin, a drug often used to lower cholesterol, is being tested for its effects on sleep apnea. Previous studies found that atorvastatin can help lower blood pressure and improve cholesterol levels in people with sleep apnea. However, it did not significantly improve blood vessel function or reduce early signs of artery clogging.

Atorvastatin is generally well-tolerated and already approved for other uses, which means its safety is well-known. However, some risks exist. For example, statins like atorvastatin have been linked to a higher chance of developing diabetes in people with certain conditions, such as high blood pressure and sleep apnea.

Overall, while atorvastatin is considered safe for most people, it's important to be aware of these potential risks, especially if other health issues are present. Always talk to a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleep apnea?

Most treatments for obstructive sleep apnea (OSA) rely heavily on Continuous Positive Airway Pressure (CPAP) therapy to keep airways open during sleep. However, researchers are excited about using atorvastatin because it targets inflammation and cholesterol, which are often elevated in OSA patients. Unlike CPAP, which mechanically assists breathing, atorvastatin could address some of the underlying cardiovascular risks associated with OSA, potentially offering a dual benefit. This unique approach might improve overall heart health in addition to managing sleep apnea symptoms.

What evidence suggests that atorvastatin combined with CPAP might be an effective treatment for sleep apnea?

Research has shown that atorvastatin, a cholesterol-lowering drug, might help reduce inflammation in people with obstructive sleep apnea (OSA). In this trial, some participants will receive atorvastatin to assess its effects on inflammation and blood vessel protection in OSA patients, even if they don't consistently use their CPAP machines. However, previous studies have shown mixed results. One study found that atorvastatin did not improve blood vessel function or reduce early signs of artery disease in these patients. Despite these mixed results, atorvastatin has been shown to lower cholesterol and inflammation, which are important for managing health issues related to OSA. ^{3 6 7 8 9}

Who Is on the Research Team?

Sanja Jelic, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults over 18 newly diagnosed with obstructive sleep apnea (OSA), characterized by frequent interruptions in breathing during sleep. Participants should not have used CPAP therapy before and must not be on regular medications or have a history of serious heart, lung, kidney diseases, diabetes, cancer, muscle issues or smoking recently.

Inclusion Criteria

I have been newly diagnosed with sleep apnea and have not used CPAP.

Exclusion Criteria

I have a history of heart, lung, kidney, rheumatic diseases, diabetes, cancer, muscle issues or I've smoked in the last 5 years.

I regularly take medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin 10 mg daily or placebo for 4 weeks to test its effects on endothelial dysfunction in OSA patients treated with CPAP

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Continuous Positive Airway Pressure Therapy
• Placebo

Trial Overview The study tests if taking Atorvastatin (a cholesterol-lowering medication) for four weeks reduces inflammation related to OSA in patients also using CPAP therapy. It's a randomized trial where some get the real medicine while others get a placebo without knowing which one they're receiving.

How Is the Trial Designed?

Group I: Treatment Active Control 2 Interventions

OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily.

Group II: Control Placebo Group 2 Interventions

OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily.

Atorvastatin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

An 8-year therapy with autoadjusting positive airway pressure (APAP) significantly reduced daytime sleepiness in patients with moderate to severe obstructive sleep apnea (OSA), indicating improved overall sleep quality.

However, the long-term APAP treatment did not lead to significant changes in fasting lipid levels, suggesting that while it benefits sleep apnea symptoms, it may not directly affect cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid profile after long-term APAP in OSA patients. Rebelo, S., Drummond, M., Marques, JA.[2018]

Atorvastatin effectively lowers LDL cholesterol levels by 41% to 61%, depending on the dosage, through its mechanism of inhibiting HMG Co-A reductase, which increases LDL receptors in the liver.

The safety profile of atorvastatin is favorable, with only transient gastrointestinal side effects and rare changes in liver tests or muscle enzymes, making it a viable option for treating various forms of hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atorvastatin (Lipitor)]. Carpentier, Y., Ducobu, J., Sternon, J.[2018]

In a multicenter trial involving 47 patients, atorvastatin significantly reduced levels of harmful lipoproteins and triglycerides after 12 weeks at both 10 mg and 20 mg doses, indicating its efficacy in managing cholesterol and triglyceride levels.

Atorvastatin not only lowered bad cholesterol (LDL-C) and triglycerides but also increased good cholesterol (HDL-C), making it a promising treatment option for patients with different types of lipid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels. Alaupovic, P., Heinonen, T., Shurzinske, L., et al.[2019]

Atorvastatin is a highly effective statin that significantly reduces low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels in patients with high cholesterol, achieving better results than other statins.

While atorvastatin is generally safe, it can cause mild side effects like gastrointestinal issues and muscle pain, and it may require monitoring for liver enzyme levels, especially due to its metabolism through the CYP3A4 pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor. Malinowski, JM.[2022]

Atorvastatin is a highly effective statin that significantly lowers LDL and total cholesterol levels, and it is the first statin proven to reduce triglycerides in patients with high triglyceride levels.

In addition to its cholesterol-lowering effects, atorvastatin has beneficial non-lipid effects, such as improving blood vessel function and reducing inflammation, although clinical trial evidence is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin. Wierzbicki, AS.[2019]

CPAP treatment for obstructive sleep apnea (OSA) significantly improves cholesterol levels by decreasing total cholesterol and low-density lipoprotein (LDL) while increasing high-density lipoprotein (HDL), based on a meta-regression analysis of 29 studies involving 1,958 subjects.

The analysis showed that while total cholesterol and LDL levels decreased significantly, triglyceride (TG) levels did not show a significant change, indicating that CPAP may specifically target certain aspects of dyslipidemia in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis. Nadeem, R., Singh, M., Nida, M., et al.[2022]

In a study of 117 patients on lipid-lowering therapy who started CPAP for obstructive sleep apnea, those with good medication adherence (≥80%) were 1.8 times more likely to use CPAP for at least 4 hours a day compared to those with low adherence.

The association between medication adherence and CPAP use was influenced by marital status, indicating that social factors may also play a role in adherence to both medications and CPAP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to sleep apnea therapy and use of lipid-lowering drugs: a study of the healthy-user effect. Platt, AB., Kuna, ST., Field, SH., et al.[2022]

Atorvastatin effectively lowers elevated levels of LDL cholesterol and triglycerides in patients with various dyslipidemic disorders, showing tailored efficacy based on the specific lipid abnormalities present in each patient group.

The drug was well-tolerated among 231 patients in the study, with a safety profile comparable to other medications in the same class, indicating it is a safe option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. Bakker-Arkema, RG., Best, J., Fayyad, R., et al.[2019]

Atorvastatin effectively lowers total cholesterol, LDL-cholesterol, and triglycerides while increasing HDL-cholesterol, making it more effective than other statins in patients with coronary heart disease (CHD).

It is well tolerated with mild and transient side effects, and long-term studies are ongoing to assess its impact on serious cardiac events and mortality, confirming its role as a first-line treatment for various patients at risk for CHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Malhotra, HS., Goa, KL.[2018]

Atorvastatin, while effective in lowering LDL cholesterol and preventing cardiovascular diseases, can lead to serious side effects such as rhabdomyolysis and acute kidney injury, particularly when used with warfarin due to shared metabolic pathways.

A case study of a 66-year-old man highlighted the risks of renal complications and muscle damage from the combination of atorvastatin and warfarin, emphasizing the need for careful monitoring of drug interactions in patients with cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhabdomyolysis due to warfarin and atorvastatin combination therapy in a patient with ischemic heart disease: (A drug interaction). Soliemanabad, SK., Rasouli, K., Zakariaei, Z., et al.[2022]

Long-term CPAP treatment significantly reduces total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in patients with severe obstructive sleep apnea (OSA), with improvements observed as early as 2 months and sustained over 5 years.

The reduction in TC and LDL-C was more pronounced in younger patients and those with higher body mass index (BMI), while CPAP therapy did not significantly affect triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 5-year continuous positive airway pressure treatment on the lipid profile of patients with obstructive sleep apnea: A pilot study. Simon, B., Gabor, B., Barta, I., et al.[2020]

Atorvastatin, administered at 40 mg daily for 15 days to 16 normolipidemic subjects, resulted in significant reductions in cholesterol levels, including a 48% decrease in LDL cholesterol, demonstrating its efficacy as a lipid-lowering agent.

The study found that atorvastatin was well tolerated and that its lipid-lowering effects were similar regardless of whether it was taken in the morning or evening, which contrasts with other similar medications that are more effective when taken at night.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening. Cilla, DD., Gibson, DM., Whitfield, LR., et al.[2019]

In a study involving 24 men with high cholesterol, lovastatin showed a potential improvement in sleep quality by reducing the number of awakenings compared to placebo, although it did not significantly differ in other sleep parameters.

Pravastatin, on the other hand, was associated with a decline in sleep quality compared to lovastatin, affecting sleep efficiency and increasing wake time, suggesting that lovastatin may be a better option for sleep-related side effects in patients taking statins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia. Partinen, M., Pihl, S., Strandberg, T., et al.[2019]

Citations

1. academic.oup.com academic.oup.com/ajh/advance-article-abstract/doi/10.1093/ajh/hpaf202/8281786

High-Intensity Atorvastatin and 24-Hour Blood Pressure in ... Our data suggest that high-intensity atorvastatin does not lower resting or ambulatory BP in patients with OSA relative to a placebo. Thus, it ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25221387/

Response to statin therapy in obstructive sleep apnea ... Conclusion: In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00669695?tab=table

Systemic Inflammation and Obstructive Sleep Apnea ... Evaluation of the inflammation occurring during OSAS. [Time Frame: after 3 months of Atorvastatin or placebo treatment.] Evaluation of the insulin-resistance ...

4. atsjournals.org atsjournals.org/doi/10.1513/AnnalsATS.202209-761OC

Annals of the American Thoracic Society Statin restores endothelial protection against complement in obstructive sleep apnea (OSA) regardless of adherence with continuous positive ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4158472/

Response to Statin Therapy in Obstructive Sleep Apnea ... In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11980143/

The use of statins are associated with an increased risk of new ... The use of statins are associated with an increased risk of new-onset diabetes in patients with hypertension and obstructive sleep apnoea, a longitudinal study.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00669695

Systemic Inflammation and Obstructive Sleep Apnea ... The aim of this clinical trial is to evaluate the effect of Atorvastatin on the endothelial function improvement during the obstructive sleep apnea syndrome ( ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03122639

Endothelial Function in Obstructive Sleep Apnea Outcome 2 will be assessed before and after 4 weeks of atorvastatin or placebo. Each patient 28-day follow-up value will be compared with baseline value. This ...

9. researchgate.net researchgate.net/publication/396422585_High-Intensity_Atorvastatin_and_24-Hour_Blood_Pressure_in_Obstructive_Sleep_Apnea_A_Randomized_Double-Blind_Placebo-Controlled_Pilot_Study

A Randomized, Double-Blind, Placebo-Controlled Pilot Study High-Intensity Atorvastatin and 24-Hour Blood Pressure in Obstructive Sleep Apnea: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.