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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how sleep apnea affects the heart, particularly in women with obesity. Researchers aim to understand why women might face a higher risk of heart problems from sleep apnea compared to men. The trial will test the body's response to low oxygen using various medications, including dexmedetomidine (a sedative), norepinephrine (which increases blood pressure), phentolamine (which blocks certain nerve signals), and phenylephrine (which narrows blood vessels). Premenopausal women with obesity may qualify if they do not have sleep apnea or certain health conditions. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking insights.

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.

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

Research has shown that the treatments in this trial have had varied safety outcomes in past studies.

Dexmedetomidine has successfully helped patients with obstructive sleep apnea relax. One study found it provided good relaxation without worsening breathing problems. Another study showed it did not negatively affect breathing patterns or oxygen levels during sleep.

Norepinephrine, often used in managing sleep apnea, has shown mixed results. It can be part of treatments that slightly improve sleep apnea symptoms, but its exact role requires further research.

Phentolamine has improved blood flow during low oxygen conditions in some studies, suggesting it might be safe for similar uses.

Phenylephrine has been tested as a nasal decongestant. It reduces nasal blockage but does not significantly change sleep-related breathing issues, suggesting it may be safe for short-term use.

Since this trial is in an early phase, the main focus is on understanding safety rather than effectiveness. Researchers closely monitor new treatments in early trials for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a unique approach to managing sleep apnea's cardiovascular impact in women with obesity. Unlike most treatments that focus on lifestyle changes and CPAP machines, these drugs—dexmedetomidine, norepinephrine, phentolamine, and phenylephrine—are administered via intra-arterial infusions and may provide immediate cardiovascular benefits. By targeting specific receptors in the body, they aim to improve blood flow and reduce stress on the heart during hypoxic conditions, which is a new mechanism of action compared to the existing standard of care. This trial could lead to a breakthrough in how we manage cardiovascular risks associated with sleep apnea.

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

In this trial, participants will receive various treatments to assess their cardiovascular impact under hypoxic conditions. Research has shown that dexmedetomidine, one of the treatments, can lower blood pressure and heart rate, potentially aiding heart issues in people with sleep apnea. Norepinephrine, another treatment option, influences heart health by altering blood pressure and heart rate patterns, which often differ in those with sleep apnea. Phentolamine, also under study, has been linked to improved heart function in individuals with heart problems, suggesting it might benefit those with sleep apnea as well. Phenylephrine, the final treatment, is known for tightening blood vessels, affecting blood flow and heart health in sleep apnea patients. While these treatments target different aspects of heart health, their combined effects in this trial may offer a new approach to managing heart risks related to sleep apnea, particularly in women with obesity. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7058802/

Dexmedetomidine Improves Cardiovascular and Ventilatory ... They found patients receiving DEX had significantly lower blood pressure and heart rate. Conversely, they also found more hypotension and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11575733/

Impact of Obstructive Sleep Apnea on Cardiovascular Health These studies consistently highlighted the significant role OSA plays in exacerbating cardiovascular risks, particularly in patients with comorbid conditions.

3. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1426729/full

Impact of mini-dose dexmedetomidine supplemented ... Conclusion: Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03624595

Low-dose Dexmedetomidine and Postoperative Delirium ... In recent studies of elderly after noncardiac surgery, night-time infusion of low-dose dexmedetomidine reduces delirium and improves 2-year survival. The ...

5. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.6592

Upper Airway Reflexes are Preserved During ... Upper airway reflexes are preserved during dexmedetomidine sedation in children with Down syndrome and obstructive sleep apnea. J Clin Sleep Med. 2017;13(5):721 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11480026/

Impact of mini-dose dexmedetomidine supplemented ... Based on our recent results, mini-dose dexmedetomidine supplemented intravenous analgesia increased the percentage of N2 sleep from 59.4% ± 25.8 ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/pan.14290

Outcomes of dexmedetomidine sedation for drug‐induced ... Conclusions. Dexmedetomidine alone or along with ketamine provided acceptable sedation in majority of the patients with obstructive sleep apnea ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945725001017

Effects of dexmedetomidine and propofol on the key ... Dexmedetomidine had less impact on OSA endotypic traits compared to propofol, and had no negative effects on AHI and SpO 2.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9471089/

Effect of low-dose dexmedetomidine on sleep quality in ... Daily results showed that dexmedetomidine only improved two RCSQ items and the overall RCSQ score on postoperative day 6. The effects of low- ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT01733043

NCT01733043 | Sedative Effects in Obstructive Sleep Apnea The objective of this study is to determine the effect of dexmedetomidine infusion on the Apnea / Hypopnea Index (AHI) of individuals with previously documented ...