res-ct page

CLINICAL TRIALS IN SLEEP DISORDERS

Pharmacologic Treatments for Sleep Apnea: Clinical Pilot Study
David W. Carley, Principal Investigator (BTG International)
Abstract

Management of Sleep-Disordered Breathing in Bariatric Surgery Patients Using the Autoset Spirit
James Herdegen, Principal Investigator (ResMed Foundation)
Abstract

Nurse-managed Cognitive Behavioral Therapy for Insomnia in Chronic Obstructive Pulmonary Disease

Abstract

Pharmacologic Treatments for Sleep Apnea: Clinical Pilot Study
It is now well established that the prevalence of clinically significant sleep related apnea increases from 3% - 5% in the general population to over 25% in the elderly (Groth, 2005). Further, if left untreated, sleep apnea syndrome increases the risk of hypertension, coronary heart disease, myocardial infarction, stroke, insulin resistance, glucose intolerance, diabetes and death (for example: Young, 2000; Punjabi, 2004). Although continuous positive airway pressure (CPAP), the current standard of therapy for most adult patients, can effectively control apnea expression in the laboratory, long-term compliance is very poor. Only about half of all patients started on CPAP use the device for more than 4 – 5 hours per night and at least 5 nights per week (for example: Kribbs, 1993; Russo-Magno, 2001; Zozula, 2001) and many patients refuse to attempt CPAP. Frequent reasons for non-compliance include: mask discomfort, nasal dryness or congestion, and difficulty tolerating the pressure. Currently, no effective medical treatment has been developed for sleep apnea syndrome. Unlike previous tests of putative drug treatments for sleep apnea, the presently proposed clinical pilot study of ondansetron+fluoxetine is based on positive preclinical results from two different animal models of sleep-related breathing disorder (Radulovacki, 1998; Carley, 1999; Veasey, 2001). Combined use of animal model systems together with clinical investigation may help provide insights necessary to the development of effective pharmacotherapies for sleep apnea and related disorders. The exact formulations being tested in this clinical trial were identified by an additional series of preclinical studies in the animal model. For example, our animal model system demonstrated a reduction in AHI of 54% when the serotonin antagonist mirtazapine was given systemically (Carley, 1999). A pilot study of mirtazapine in patients with OSA demonstrated AHI reductions of 48% and 52% for oral doses of 4.5 mg and 15 mg QD, respectively (Carley, Sleep Med 4:S6, 2003).

A Randomized, Double-blind, Placebo-controlled, Multicenter Parallel-Group Dose Ranging Clinical Trial to Assess the Efficacy and Safety of Org 4419-2 in the Treatment of Obstructive Sleep Apnea Syndrome
It is now well established that the prevalence of clinically significant sleep related apnea increases from 3% - 5% in the general population to over 25% in the elderly (Groth, 2005). Further, if left untreated, sleep apnea syndrome increases the risk of hypertension, coronary heart disease, myocardial infarction, stroke, insulin resistance, glucose intolerance, diabetes and death (for example: Young, 2000; Punjabi, 2004). Although continuous positive airway pressure (CPAP), the current standard of therapy for most adult patients, can effectively control apnea expression in the laboratory, long-term compliance is very poor. Only about half of all patients started on CPAP use the device for more than 4 – 5 hours per night and at least 5 nights per week (for example: Kribbs, 1993; Russo-Magno, 2001; Zozula, 2001) and many patients refuse to attempt CPAP. Frequent reasons for non-compliance include: mask discomfort, nasal dryness or congestion, and difficulty tolerating the pressure. Currently, no effective medical treatment has been developed for sleep apnea syndrome. Unlike previous tests of putative drug treatments for sleep apnea, the presently proposed clinical pilot study of ondansetron+fluoxetine is based on positive preclinical results from two different animal models of sleep-related breathing disorder (Radulovacki, 1998; Carley, 1999; Veasey, 2001). Combined use of animal model systems together with clinical investigation may help provide insights necessary to the development of effective pharmacotherapies for sleep apnea and related disorders. For example, our animal model system demonstrated a reduction in AHI of 54% when the serotonin antagonist mirtazapine was given systemically (Carley, 1999). A pilot study of mirtazapine in patients with OSA demonstrated AHI reductions of 48% and 52% for oral doses of 4.5 mg and 15 mg QD, respectively (Carley, Sleep Med 4:S6, 2003). The current trial is a multicenter international study designed to test the benefits of mirtazapine in a larger and medically more diverse group of patients with sleep disordered breathing.

Management of Sleep-Disordered Breathing in Bariatric Surgery Patients Using the Autoset Spirit
Obesity is a well-established risk factor for sleep apnea syndrome and anecdotal evidence indicates that sustained weight loss can reverse or eliminate sleep apnea in some cases. This study will employ the Autoset Spirit, a continuous positive airway pressure system with the ability to automatically determine and adjust the required therapeutic pressure level, to correlate apnea severity with weight loss following bariatric surgery. It is hypothesized that required pressure levels will decrease, in some cases to zero, with ongoing weight loss.