Sleep Disorders clinical trials at University of California Health

Obstructive sleep apnea (OSA) is a severe type of snoring causing people to choke in their sleep. It affects millions of Americans, causing many health problems. For example, patients with OSA often feel very sleepy and are at risk of falling asleep while driving. OSA also causes elevated blood pressure increasing the risk for heart attacks and strokes. Patients with OSA are often treated with a face-mask that helps them breath at night but can be difficult to tolerate. In fact, about half the patients eventually stop using this mask. Because there are few other treatments (and no drug therapy), many OSA patients are still untreated. Of note, especially young adults (i.e. 18 to 50 years old) benefit from treating their OSA, but they are also less likely to use the mask. Acetazolamide (a mild diuretic drug) has been used for over 50 years to treat many different conditions and is well tolerated. Recent data suggest, that acetazolamide may help OSA patients to not choke in their sleep and lower their blood pressure. Especially young adults with OSA are likely to respond well to this drug. Further, its low cost (66¢/day) and once- daily dosing may be particularly attractive for young OSA patients unable or unwilling to wear a mask each night. But previous studies had many limitations and did not focus on young adults. The goal of this study is to test if acetazolamide can improve sleep apnea and cardiovascular health in young adults with OSA (18-50 years old), and how it does that. Thus, we will treat 46 young OSA patients with acetazolamide or placebo for 2 weeks each. The order in which participants receive the drug or placebo will be randomized. At the end of each 2 week period we will assess OSA severity and cardiovascular health. Thus, this study will help assess acetazolamide's potential value for OSA treatment, and may also help to identify patients who are most likely to respond to acetazolamide (including select individuals >50 years of age). Ultimately, this work promises a drug therapy option for millions of OSA patients who are unable to tolerate current treatments.

Insomnia is a common condition in Veterans, with prevalence rates as high as 53% among treatment-seeking Veterans. Chronic untreated insomnia is associated with increased risk for functional impairment, psychiatric illness, suicidal ideation, unhealthy lifestyles, and decreased quality of life. Cognitive-Behavioral Therapy for Insomnia (CBT-I) is recognized as the first-line treatment for insomnia. Despite its proven efficacy, CBT-I is not always readily provided and/or accessible to Veterans. To address these limitations, behavioral sleep medicine specialists have endeavored to streamline CBT-I through development of time-shortened variations of CBT-I. Although these modifications show promise for advancing care and access, studies comparing brief treatments to standard CBT-I have yet to be performed. This investigation will therefore compare a 4-session brief CBT-I to VA standard 6-session CBT-I to evaluate whether a brief intervention can provide comparable benefits to sleep, functional, and psychiatric outcomes in Veterans with insomnia.

This study will investigate why some people have Obstructive Sleep Apnea (OSA) and how the underlying cause may relate to OSA manifestations (including sleepiness and high blood pressure) and response to different therapeutic approaches (ie CPAP, eszopiclone, and supplemental oxygen). Understanding why someone has OSA could affect how best to treat that individual, but may also have an impact on what problems the disease might cause.

The primary medical therapies for patients with Obstructive Sleep Apnea syndrome (OSA) require the use of medical devices on a nightly basis to help control breathing during sleep, which can be difficult for patients with mild-to-moderate disease. Because many patients use these therapies on a limited basis, or stop using them altogether, they continue to be at increased risk of the consequences of untreated OSA. Untreated and undertreated OSA compounds the risk of OSA consequences over time, particularly with increasing age and weight. Orofacial Myofunctional Therapy (OMT) takes a rehabilitative approach to OSA and is comprised of isotonic and isometric exercises that target the oral (e.g., tongue) and oropharyngeal (e.g., soft palate, lateral pharyngeal wall) to help restore normal breathing and airway patency at night while asleep. Should the study have positive findings, OMT could become an important alternative therapy for patients with mild-to-moderate disease because patients could utilize a therapy that improves their nighttime breathing through daytime exercises and without the need for a burdensome medical device.

More than 10% of the US population have obstructive sleep apnea (OSA). Standard of care is therapy with CPAP (continuous positive airway pressure) which virtually eliminates OSA. However, most patients use CPAP only for part of the night (4-5hours) and about 50% patients discontinue CPAP long-term. Alternative therapies are limited, thus many OSA patients remain at risk of OSA sequelae (e.g. sleepiness, memory issues, high blood pressure, etc.). Importantly, different patients get OSA for different reasons, and recent data show that some of the underlying causes of OSA ("endotypes") such as having a low arousal threshold (i.e. waking up easily) are associated with lower CPAP adherence. Using a randomized controlled trial design, this will be the first study using a targeted intervention to manipulate the underlying OSA causes (i.e., giving a safe hypnotic to patients with OSA to increase the arousal threshold) to test the hypothesis that endotype-targeted therapy increases CPAP-adherence in patients who have low but continued CPAP usage. Ultimately, this strategy may improve the care and outcomes of millions of undertreated OSA patients.

To evaluate the safety and effectiveness of the Automatic Expiratory Positive Airway Pressure (Auto-EPAP) feature versus manual expiratory positive airway pressure (EPAP) in the Vivo 45 LS Ventilator.

Obstructive sleep apnea (OSA) is common in older adults and has recently been implicated in pathogenesis of Alzheimer's disease (AD). Research has shown that sleep disruptions have caused memory impairment. Sleep apnea is a form of sleep disruption. We would like to examine how obstructive sleep apnea may contribute to the progression of Alzheimer's disease.

Patients with chronic pain who use opioids appear to be at increased risk for breathing issues during sleep, termed sleep disordered breathing (SDB). Treatment of SDB often consists of use of a device during sleep that provides continuous positive airway pressure (CPAP) via a mask interface. However, this device is not effective or tolerated in all individuals. The goal of this study is to examine whether a medication called acetazolamide can improve SDB, as an alternative to CPAP treatment. The investigators will measure the improvement in SDB, as well as any change in symptoms, during a 1 week treatment with acetazolamide compared with 1 week of placebo (sugar pill). This study will help to provide data for longer term studies of treatment for SDB in patients who use opioids.

Substance use disorder (SUD) and posttraumatic stress disorder (PTSD) frequently co-occur and having both disorders is associated with greater psychological and functional impairment than having either disorder alone. This is especially true in residential settings where both disorders are more severe than outpatient settings. Obstructive sleep apnea (OSA) is highly comorbid with both disorders and untreated OSA is associated with worse functional impairment across multiple domains, worse quality of life, worse PTSD, higher suicidal ideation, and higher substance use and relapse rates. Treating OSA with evidence-based positive airway pressure (PAP) in Veterans with SUD/PTSD on a residential unit is a logical way to maximize treatment adherence and treatment outcomes. This study compares OSA treatment while on a SUD/PTSD residential unit to a waitlist control group. The investigators hypothesize that treating OSA on the residential unit, compared to the waitlist control, will have better functional, SUD, and PTSD outcomes.

Obstructive sleep apnea (OSA) is a severe type of snoring causing people to choke in their sleep. It affects millions of Americans, causing many health problems. For example, patients with OSA often feel very sleepy and are at risk of falling asleep while driving. OSA also causes elevated blood pressure, memory problems and can severely affect quality of life. Patients with OSA are often treated with a face-mask that helps them breath at night but can be difficult to tolerate. In fact, about half the patients eventually stop using this mask. Because there are few other treatments (and no drug therapy), many OSA patients are still untreated. Acetazolamide (a mild diuretic drug) has been used for over 50 years to treat many different conditions and is well tolerated. Recent data suggest, that acetazolamide may help OSA patients to not choke in their sleep and lower their blood pressure. Further, its low cost (66¢/day) and once-daily dosing may be attractive for OSA patients unable or unwilling to wear a mask each night. But previous studies had many limitations such as studying acetazolamide for only a few days and not capturing important outcomes. The goal of this study is to test if acetazolamide can improve sleep apnea, neurocognitive function and quality of life in adults with OSA, and to assess how it does that. Thus, the investigators will treat 60 OSA patients with acetazolamide or placebo for 4 weeks each. The order in which participants receive the drug or placebo will be randomized. At the end of each 4 week period the investigators will assess OSA severity, neurocognitive function and quality of life. Thus, this study will help assess acetazolamide's potential value for OSA treatment, and may also help to identify patients who are most likely to respond to acetazolamide. Ultimately, this work promises a drug therapy option for millions of OSA patients who are unable to tolerate current treatments

Major progress has been made in the area of cardiovascular disease, but we believe that further progress will involve mechanistically addressing underlying respiratory causes including chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). The most common cause of death in COPD is cardiovascular, although mechanisms are unknown. OSA has been associated with major neurocognitive and cardiovascular sequelae, the latter likely a function of autonomic nervous system abnormalities, oxidative stress, inflammation, and other pathways. Recent data suggest that individuals with OVS die preferentially of cardiovascular disease compared to OSA or COPD alone, although mechanisms are again unclear. The combination of OSA and COPD may lead to profound hypoxemia. Individuals with COPD can develop pulmonary hypertension via disturbances in gas exchange and parenchymal injury leading to loss of pulmonary vasculature. OSA has been associated with mild to moderate pulmonary hypertension, but the situation may be worse if combined with parenchymal lung disease. The biological response to sustained hypoxemia has been carefully studied as has the topic of intermittent hypoxemia; however, to our knowledge, very little research has occurred regarding the combination of sustained plus intermittent hypoxia as seen in OVS. For example, we do not really know whether individuals with OVS develop coronary disease, right or left heart failure, dysrhythmias or some combination of abnormalities predisposing them to cardiovascular death. Thus, design of interventional studies is challenging as causal pathways are poorly understood despite our considerable preliminary data addressing these issues. The purpose of this study is to examine vascular mechanisms in individuals with COPD/OSA overlap syndrome (OVS) compared with matched individuals with obstructive sleep apnea (OSA) alone or chronic obstructive pulmonary disease (COPD) alone and to perform a phase II pilot mechanistic clinical trial in OVS to examine the effect size of nocturnal bi-level positive airway pressure (PAP) vs. nocturnal oxygen therapy in cardiovascular outcomes.

Obstructive sleep apnea (OSA) is a highly prevalent disorder that is associated with both cardiovascular and metabolic dysfunction, such as hypertension, increased blood glucose levels and diabetes, obesity, and nonalcoholic fatty liver. While continuous positive airway pressure (CPAP), the best available OSA treatment, has been shown to improve blood pressure in OSA, it does not appear to improve metabolic consequences of OSA, and other therapies for OSA-induced dysmetabolism are needed. Animal models of time restricted eating (TRE) demonstrate an improvement in glucose and lipid metabolism, even in the absence of a reduction of caloric intake. Some human studies have shown an improvement in metabolic dysfunction with TRE, though further well-designed studies are needed. The effects of TRE on metabolic dysfunction in patients with OSA, a population with a high predisposition to metabolic disorder, has never been examined. In this study, we will conduct a randomized clinical trial to assess the feasibility and efficacy of 12 weeks of TRE, versus standard eating (SE), to improve glucose regulation and cardiovascular health of participants with OSA.