Sleep Apnea's Cardiovascular Impact on Women With Obesity

Overseen By Jacqueline K Limberg, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Missouri-Columbia

Must not be taking: Prescription medications

Disqualifiers: Pregnancy, Smoking, Cardiovascular, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

104 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial excludes participants who are currently taking prescription medications, so you would need to stop taking them to participate.

What data supports the effectiveness of the drug for sleep apnea in women with obesity?

A systematic review and meta-analysis found that combined noradrenergic plus antimuscarinic agents significantly improved sleep apnea symptoms, such as reducing the number of breathing interruptions during sleep and increasing oxygen levels, compared to a placebo. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The research suggests that phenylephrine, a component of the treatment, is generally safe for people with controlled high blood pressure. However, caution is advised for those with hypertension, as some components can raise blood pressure. ^{1 3 4 6 7}

How does the treatment for sleep apnea in women with obesity differ from other treatments?

The treatment for sleep apnea in women with obesity likely involves continuous positive airway pressure (CPAP), which is unique because it uses a nasal mask to keep the airway open during sleep, reducing apnea episodes and improving cardiovascular health. This is different from other treatments that might not directly address the airway obstruction or provide the same cardiovascular benefits. ^{8 9 10 11 12}

What is the purpose of this trial?

Patients with sleep apnea are at increased risk of developing cardiovascular disease - with women at potentially greater risk than men. Contributing mechanisms are not well understood, but may be related to how women respond to low oxygen and, given over 70% of patients with sleep apnea are obese, the impact of obesity. This project seeks to increase our understanding of mechanisms that may contribute to sex differences in the cardiovascular response to low oxygen with the hope that this knowledge will improve the efficacy of current therapies and support the discovery of novel therapeutics.

Eligibility Criteria

This trial is for premenopausal women aged 18-45, who are either obese (BMI ≥30) or of healthy weight (BMI between 18 and ≤25). Participants should not have sleep apnea, cardiovascular issues, clotting disorders, high blood pressure, diabetes, PCOS, communication barriers or be using certain medications including oral contraceptives.

Inclusion Criteria

My BMI is 30 or higher.

I am between 18 and 45 years old and have not gone through menopause.

My BMI is between 18 and 25.

Exclusion Criteria

I have sleep apnea or my oxygen levels drop frequently at night.

You are currently smoking or using nicotine products.

I am not pregnant, breastfeeding, or using oral hormonal contraceptives.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hypoxia Exposure

Participants undergo intra-arterial pharmacological infusions under normoxic and hypoxic conditions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexmedetomidine
• Norepinephrine
• Phentolamine
• Phenylephrine

Trial Overview The study investigates how low oxygen levels affect the cardiovascular system differently in men and women and if obesity influences this. It involves drugs like Phentolamine and Norepinephrine to study blood vessel responses under hypoxic conditions.

Participant Groups

Group I: Hypoxia Exposure Experimental Treatment 5 Interventions

A physician will place a catheter in the brachial artery for intra-arterial pharmacological infusions. The following drugs will be administered to each participant under room air (normoxic) and low oxygen (hypoxic) conditions: phenylephrine, dexmedetomidine, norepinephrine, phentolamine (see Interventions for details).

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Findings from Research

A review of 12 clinical studies found that intranasal phenylephrine appears to be safe for patients with controlled hypertension, based on one double-blind randomized trial.

The evidence regarding the safety of other sympathomimetic decongestants like phenylpropanolamine and pseudoephedrine in hypertensive patients is limited and unclear, suggesting that the belief they are unsafe is not strongly supported by research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are oral decongestants safe in hypertension? An evaluation of the evidence and a framework for assessing clinical trials. Radack, K., Deck, CC.[2013]

Hypertensive patients should avoid using adrenergic agents for blood pressure control, with nasal phenylephrine hydrochloride being the safest option among them, while pseudoephedrine may also be safe.

Ibuprofen can raise blood pressure if taken at maximum over-the-counter doses for extended periods, highlighting the need for caution with nonprescription medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonprescription drugs and hypertension. Which ones affect blood pressure? Bradley, JG.[2019]

A systematic review of nine randomized controlled trials found that combining noradrenergic and antimuscarinic agents significantly reduced the severity of obstructive sleep apnea (OSA), as indicated by improvements in the sleep apnea-hypopnea index and oxygen saturation levels.

While this drug combination showed promise in improving OSA symptoms after a single night of treatment, further research is needed to assess the long-term efficacy and safety of these medications for OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined noradrenergic plus antimuscarinic agents for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials. Zha, S., Yang, H., Yue, F., et al.[2022]

In a study measuring the effects of 60 mg pseudoephedrine and pseudoephedrine-triprolidine taken four times a day for 5 days, neither medication showed any impairment in night vision, color perception, stereopsis, or reaction time.

These results suggest that both pseudoephedrine and pseudoephedrine-triprolidine are safe in terms of cognitive and visual performance when used as directed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of pseudoephedrine and triprolidine on visual performance. Luria, SM., Paulson, HM., Ryan, AP., et al.[2013]

A study involving 28 volunteers with controlled hypertension found that sustained-release pseudoephedrine (120 mg twice daily) did not cause statistically significant changes in blood pressure or heart rate, suggesting it may be safe for use in these patients.

However, there was a noted upward trend in mean arterial pressure and heart rate over time, indicating that further research in a larger population may be necessary to fully assess the cardiovascular safety of pseudoephedrine in hypertensive individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of pseudoephedrine in medically controlled hypertensive patients. Beck, RA., Mercado, DL., Seguin, SM., et al.[2015]

In a study of 56 patients with allergic rhinitis, the combination of Loratadine and Pseudoephedrine Sulfate Repetabs (LTD+PSE) was found to be well tolerated with fewer adverse effects compared to the standard loratadine plus pseudoephedrine treatment.

Specifically, the incidence of tremors was significantly lower in the LTD+PSE group (10.7%) compared to the loratadine plus pseudoephedrine group (39%), indicating that LTD+PSE may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of the side effects between pseudoephedrine in Loratadine plus Pseudoephedrine Sulfate Repetabs Tables and loratadine + pseudoephedrine tablet in treatment of allergic rhinitis in Thai patients. Supiyaphun, P., Chochaipanichnon, L., Kerekhanjanarong, V., et al.[2013]

Sympathomimetic decongestants, commonly found in cold medications, can raise blood pressure, which poses a risk for patients with hypertension.

Due to the potential for adverse effects, particularly with agents like phenylephrine and pseudoephedrine, it is advisable for individuals with high blood pressure to avoid these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs for cough and cold symptoms in hypertensive patients. White, WB., Riotte, K.[2013]

Obstructive sleep apnea (OSA) is a significant risk factor for cardiovascular diseases, including hypertension and heart failure, and is closely linked to obesity and other metabolic issues.

The standard treatment for OSA, continuous positive airway pressure (CPAP), effectively eliminates apnea and improves heart function and blood pressure, yet many cases remain undiagnosed due to low physician awareness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea and cardiovascular disease. Lattimore, JD., Celermajer, DS., Wilcox, I.[2022]

Obstructive sleep apnea (OSA) is more prevalent in men than women, particularly affecting obese middle-aged men, and is linked to increased cardiovascular risk.

The editorial will explore how gender may influence cardiovascular risk markers and events in OSA patients, as well as the effects of OSA treatment on cardiovascular outcomes in both men and women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular impact of obstructive sleep apnea: does gender matter? Jenner, R., Lorenzi-Filho, G., Drager, LF.[2014]

In a study of 39 patients with severe obstructive sleep apnea (OSA), the use of CPAP on the first night significantly decreased heart rate variability (HRV), particularly during non-REM sleep, indicating an acute effect on cardiac function.

The study found that gender and obesity did not influence the changes in heart rate or HRV after CPAP treatment, suggesting that the benefits of CPAP are consistent across different patient demographics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the heart rate variability in patients with obstructive sleep apnea and its response to acute CPAP treatment. Kufoy, E., Palma, JA., Lopez, J., et al.[2021]

Obstructive sleep apnea (OSA) is linked to serious cardiovascular issues such as hypertension, coronary artery disease, and heart failure, emphasizing the need for effective screening and treatment.

Continuous positive airway pressure (CPAP) therapy may help mitigate some of the cardiovascular risks associated with OSA, but further research is needed to understand its effects on conditions like dyslipidemia and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea, hypertension and cardiovascular diseases. Gonzaga, C., Bertolami, A., Bertolami, M., et al.[2018]

Obstructive sleep apnea (OSA) significantly increases the risk of serious cardiovascular complications, including heart failure and hypertension, affecting about 5% of women and 15% of men in middle age.

Continuous positive airway pressure (CPAP) therapy is the gold standard treatment for OSA, which can help improve cardiovascular health and prevent further complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular diseases in obstructive sleep apnea. Dursunoğlu, D., Dursunoğlu, N.[2017]

References

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

Are oral decongestants safe in hypertension? An evaluation of the evidence and a framework for assessing clinical trials. [2013]

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

Nonprescription drugs and hypertension. Which ones affect blood pressure? [2019]

3. England pubmed.ncbi.nlm.nih.gov

Combined noradrenergic plus antimuscarinic agents for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials. [2022]

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

Effects of pseudoephedrine and triprolidine on visual performance. [2013]

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

Cardiovascular effects of pseudoephedrine in medically controlled hypertensive patients. [2015]

6. Thailand pubmed.ncbi.nlm.nih.gov

A comparative study of the side effects between pseudoephedrine in Loratadine plus Pseudoephedrine Sulfate Repetabs Tables and loratadine + pseudoephedrine tablet in treatment of allergic rhinitis in Thai patients. [2013]

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

Drugs for cough and cold symptoms in hypertensive patients. [2013]

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

Obstructive sleep apnea and cardiovascular disease. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Cardiovascular impact of obstructive sleep apnea: does gender matter? [2014]

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

Changes in the heart rate variability in patients with obstructive sleep apnea and its response to acute CPAP treatment. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea, hypertension and cardiovascular diseases. [2018]

12. Turkey pubmed.ncbi.nlm.nih.gov

Cardiovascular diseases in obstructive sleep apnea. [2017]