Comparing Fluticasone-salmeterol in Chronic Obstructive Pulmonary Disease (COPD) and Sleep

Study Overview
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Brief Summary
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Fluticasone (Advair), an inhaled corticosteroid and salmeterol, a long-acting beta agonist, are approved for use in the management of COPD. Fluticasone/salmeterol has been shown to significantly improve forced expiratory volume (FEV1) and decrease COPD symptoms (Calverley et al. 2003, 2007). Inhaled corticosteroids have been shown to decrease frequency of COPD exacerbations (Gartlehner et al. 2006) and long acting bronchodilators demonstrated a reduction in dyspnea, increased airflow and reduction in hyperinflation in patients with symptomatic COPD (Ramirez-Venegas et al. 1997). Specifically, salmeterol has also been shown to have a positive effect on symptoms and health status of patients with COPD when added to usual treatment (Stockley et al. 2006). Previous research of subjects from our group with asthma has shown salmeterol to be associated with sustained improvements in morning peak expiratory flow (PEF), protection from nighttime lung function deterioration and improvement in patient perception of sleep (Wiegand et al. 1999). This study has not been performed in patients with COPD nor has the effect of salmeterol with fluticasone on sleep quality been assessed. AIM: The aim of this study is to determine the effect of fluticasone/salmeterol on sleep quality in patients with COPD and to compare efficacy of Advair 250 compared to placebo on sleep. The hypothesis is that there would be a significant improvement in sleep quality when patients are placed on fluticasone/salmeterol as compared to placebo.

Detailed Description
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RATIONALE: Chronic obstructive pulmonary disease (COPD) is a term that describes a disease state in which there is chronic irreversible airflow limitation. It has been well documented that patients with COPD have disturbed sleep. Certain published reports suggest that more than 50% of COPD patients have sleep complaints (George et al., Drugs, 2003). These patients are found to have sleep onset latency and poor sleep maintenance. While their sleep disturbance may be explained in part by side effects of medications, it could also be a result of nocturnal gas exchange abnormalities (Knutty 2004). In COPD there is worsening hypoxemia and hypercapnia during sleep, particularly rapid eye movement (REM) sleep, and sleep disturbance seems to be worse with more severe COPD. It is commonly believed that optimizing medical management of the disease is important in improving the sleep quality of these patients and thus leading to improved quality of life. Fluticasone, an inhaled corticosteroid and salmeterol, a long-acting beta agonist, are approved for use in the management of COPD. Fluticasone/salmeterol has been shown to significantly improve FEV1 and decrease COPD symptoms (Calverley et al. 2003, 2007). Inhaled corticosteroids have been shown to decrease frequency of COPD exacerbations (Gartlehner et al. 2006) and long acting bronchodilators demonstrated a reduction in dyspnea, increased airflow and reduction in hyperinflation in patients with symptomatic COPD (Ramirez-Venegas et al. 1997). Specifically, salmeterol has also been shown to have a positive effect on symptoms and health status of patients with COPD when added to usual treatment (Stockley et al. 2006). Previous research of subjects from our group with asthma has shown salmeterol to be associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration and improvement in patient perception of sleep (Wiegand et al. 1999). This study has not been performed in patients with COPD nor has the effect of salmeterol with fluticasone on sleep quality been assessed. AIM: The aim of this study is to determine the effect of fluticasone/salmeterol on sleep quality in patients with COPD and to compare efficacy of Advair 250 compared to placebo on sleep. The hypothesis is that there would be a significant improvement in sleep quality when patients are placed on fluticasone/salmeterol as compared to placebo.

Official Title
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TITLE: Double-blinded, Double-dummy, Study Comparing Fluticasone-salmeterol to Placebo in Patients With COPD and Associated Poor Sleep or Daytime Somnolence.

Conditions
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COPD

Intervention / Treatment
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* Drug: Advair 250
* Drug: Placebo- matched
* Drug: Placebo
* Drug: Advair 250 - matched


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with moderate to severe COPD as per GOLD criteria Insomnia, poor sleep, non-restorative sleep or daytime sleepiness by history Age 45 to 75 years, male or female FEV1 below 80% of predicted using CRAPO FEV1/FVC < 70% predicted Past or present tobacco smoker Female patients must be postmenopausal for 1 year or be willing to use birth control or abstain from sex. Exclusion Criteria: Asthma Use of oral or injectable corticosteroids within 2 months Previous diagnosis of sleep disorder breathing (sleep apnea, narcolepsy, etc.) Lung or heart disease except for COPD Deviated nasal septum, nasal polyps or anatomic obstruction of the nose Obesity defined as BMI >30kg/m2 Inability to tolerate or history of allergy to long acting beta agonist or inhaled corticosteroid therapy. Inability to complete a 2 week run-in with albuterol prn as only therapy Use of narcotics, sleep aids, sedating antihistamines, sedatives, MAO Inhibitors, and other medications known to affect daytime somnolence or sleep quality Excessive use of alcohol or use of recreational drugs Use of narcotics, sleep aids, sedatives or sedating antihistamines. Night shift workers Women who are breast feeding or pregnant.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo, then Advair 250- matched<br>1 puff bid Placebo for two weeks followed by a 4 week washout period with placebo. After the washout period, they then received Advair 250- matched 1 puff bid for two weeks. | Drug: Advair 250<br>* 1 puff bid inhaled<br>* Other names: fluticasone/salmeterol 250/50;Drug: Placebo- matched<br>* 1 puff bid inhaled<br>|
| Active Comparator: Advair 250, then Placebo- matched<br>1 puff bid Advair 250 for two weeks followed by a 4 week washout period with placebo. After the washout period, they then received Placebo- matched 1 puff bid for two weeks. | Drug: Placebo<br>* Placebo 1 puff bid inhaled<br>Drug: Advair 250 - matched<br>* i puff bid inhaled<br>* Other names: fluticasone/salmeterol 250/50;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Aim of This Study is to Determine the Effect of Fluticasone/Salmeterol on Sleep Quality in Patients With COPD and to Compare Efficacy of Advair 250 Compared to Placebo on Sleep. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daytime Somnolence |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, sleep, daytime somnolence