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305 EVALUATION OF A LOW-COST ORAL APPLIANCE: A PILOT STUDY
S82
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
there was an improvement in the domain of bodily pain. This finding could be explained by the association of OSAS with the inflammatory processes that cause pain, which can be reversed with treatment. Support: AFIP, FAPESP (2007/06232-0), CNPq
303
PERIPHERAL VASOCONSTRICTION AND NOCTURNAL BLOOD PRESSURE CONTROL IN HYPERTENSIVE SLEEP APNEA PATIENTS
D. Zou 1 , L. Grote 1 , D.N. Eder 1 , J. Radlinski 2 , Y. Peker 3 , J. Hedner 1 . 1 Sleep Laboratory, Department of Pulmonary Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 2 Department of Pathophysiology of Respiratory System, Institute for Tuberculosis and Lung Diseases Rabka-Zdrój Branch, Rabka-Zdrój, Poland; 3 Sleep Medicine Unit, Department of Neurology and Rehabilitation Medicine, Skaraborg Hospital, Skövde, Sweden Objective: Pulse wave attenuation that occurs in association with obstructive sleep apnea (OSA) is sympathetically mediated. Doxazosin (DO) is a peripheral α-receptor inhibitor, and Enalapril (EN) is an ACE inhibitor. The aim of this study was to compare the effects of DO and EN on digital vasoconstriction and nocturnal blood pressure (BP) control in hypertensive OSA patients. Methods: A double-blind crossover study on DO (4 mg/day for 2 weeks, followed by 8 mg/day for an additional 2 weeks) and EN (10 mg/day and 20 mg/day, respectively) was undertaken in 14 OSA patients with hypertension. The patients had a mean age of 55±7 years and a mean body mass index of 30.1±3.8 kg/m2 . The patient assessment, which was performed at the end of each treatment period, included ambulatory 24-hour BP, a full-night polysomnography with simultaneous peripheral arterial tonometry (PAT) and beat-to-beat finger BP monitoring (Finapres). Nighttime BP and digital vasoconstrictions, which are associated with apneic events and are measured by the PAT ratio, were analyzed. Results: There was no difference between the two treatments for either the 24-hour BP profile or the severity of OSA. There was, however, a significant difference between the DO and EN treatments with respect to the nighttime beat-to-beat finger BP (systolic BP 129±13 vs. 119±23 mmHg, P=0.02; diastolic BP 81±12 vs. 74±14 mmHg, P=0.04). In a linear mixed effects regression model, the PAT ratio increased 8.3% after treatment with DO compared to treatment with EN (P<0.0001). Each percentage of SaO2 desaturation and each second of apnea length were associated with a 0.7% and 0.3% decrease in the PAT ratio, respectively (P<0.0001). REM sleep was associated with a 2.7% increase in the PAT ratio in contrast to that of NREM sleep. Conclusion: Digital vasoconstriction that is associated with apneic events is α-receptor mediated. DO appear to have a proportionally worse effect on nocturnal BP control when compared with that of EN in hypertensive OSA patients.
Treatment Outcome Clinical Trial Research
304
A RANDOMIZED, DOUBLE-BLIND, 6-WEEK, DOSE-RANGING STUDY OF PREGABALIN IN SUBJECTS WITH RESTLESS LEGS SYNDROME
R. Allen 1 , C. Chen 2 , A. Soaita 2 , C. Wohlberg 3 , L. Knapp 2 , D. Garcia-Borreguero 4, J. Miceli 2 . 1 Johns Hopkins Department of Neurology, Baltimore, MD, USA; 2 Pfizer Global Research and Development, New London, CT, USA; 3 Pfizer Global Research and Development, New York, NY, USA; 4 Sleep Research Institute, University of Madrid, Madrid, Spain Introduction: Clinical data suggest pregabalin as a potential treatment for primary restless legs syndrome (RLS). Objectives: To characterize the dose-response relationship of pregabalin with respect to both efficacy and safety, in patients with idiopathic RLS. Methods: This was a 6-week, randomized, double-blind, placebo-controlled, dose-ranging study of pregabalin in adults with moderate to severe idiopathic RLS. Eligible patients were randomly assigned a fixed-dose pregabalin 50, 100, 150, 300, and 450 mg/day or a placebo. Assessments were conducted at baseline and in weeks 1, 2, 4, and 6. The primary endpoint was change from baseline to week 6 in the International Restless Legs Syndrome Scale
(IRLS) total score. Secondary endpoints included Clinical Global Impressions - Improvement Scale (CGI-I) responders, sleep assessments, other global and quality of life assessments and safety/tolerability. Results: A total of 137 patients participated in the study, randomly distributed into 6 similar-sized groups. At baseline, mean (SD) IRLS total scores for placebo, 50, 100, 150, 300, and 450 mg/day pregabalin groups were 23.8 (7.2), 24.6 (6.7), 25.3 (6.4), 26.2 (7.4), 25.0 (7.4), and 24.1 (7.8), respectively; the least square mean (SE; P value) differences in change from baseline to week 6 in IRLS total score (pregabalin vs. placebo) were -4.1 (2.5; P=0.0983), -4.0 (2.4; P=0.0966), -8.3 (2.5; P=0.0013), -5.2 (2.4; P=0.0353), and -8.5 (2.5; P=0.0006), respectively. From the dose-response analysis, a pregabalin dose of 123.9 mg/day was estimated to produce a 90% maximal effect in reducing RLS symptoms. Predicted mean changes from baseline to week 6 in IRLS scores using a dose response E-max model indicated that pregabalin doses of 100 to 450 mg/day corresponded to at least an average 13.6 point-reduction (at least an average 6-point placebo-corrected treatment difference). The percentage of CGI-I responders was numerically greater among patients who received pregabalin 300 or 450 mg/day compared with patients receiving placebo or lower doses of pregabalin at the last observation. The most common adverse events were dizziness, somnolence, fatigue, dry mouth and headache. Conclusions: This dose-ranging study showed that pregabalin reduced RLS symptoms in a dose-related manner with doses >150 mg/day providing significant symptom reduction. Pregabalin was safe and well tolerated across the entire dosing range. Support: Funded by Pfizer Inc.
305
EVALUATION OF A LOW-COST ORAL APPLIANCE: A PILOT STUDY
J.J. Cervo 1 , R.C. Langien 1 , S.C. Fagondes 2 , S.W. Samuel 1 , M.L. Grossi 3 , S.S. Menna Barreto 2 . 1 UFRGS; 2 HCPA; 3 PUCRS Introduction: Oral appliances (OA) are recommended for primary snoring and for patients with mild to moderate obstructive sleep apnea (OSA). They do have some advantages over CPAP treatment such as improved comfort and lower costs. OSA is an increasing public health problem, thus, concerns about the economical aspects of its treatment are very important, especially in Brazil, a developing country. The purpose of this study was to investigate the efficacy of a modified monobloc OA made with inexpensive materials for the treatment of patients with mild to moderate OSA, for further investigation. Methods: Five male patients with BMI less than 30 kg/m2 and an apnea/hypopnea index (AHI) less than 30 events/h according to the baseline polysomnography (PSG) were treated with a low-cost modified monobloc OA. They used the OA during a mean period of 86,8±4,21 nights. A second PSG was performed with patients using the OA. The following variables were evaluated: AHI, average oxygen saturation (SpO2), minimum SpO2 (nadir SpO2) and subjective daytime sleepiness evaluation (Epworth Sleepiness Scale). Results: The mean BMI was 28,6±0,39 kg/m2 and mean age was 51,8 years old (range 46 to 60 years old). PSG showed statistically significant mean reduction of 83,5%, from baseline AIH (11,26±4,12 events/h) to AHI with OA (2,31±2,23 events/h). Nadir SpO2 increased from 86±3,4 to 90,4±1,3, with a mean increase of 4,87%. The average SpO2 did not change for the two groups. There was a mean reduction of one point in the Epworth Sleepiness Scale (Signal Test, p<0,05). No clinical complication was noticed in any participant, on teeth or soft tissues. Conclusion: This easy assembly and low-cost modified model of OA improved the outcomes and presented no complications in a small group of OSA patients and may be an appropriate alternative to be used in a larger investigation.
306
THE INFLUENCE OF TREATMENT BY CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) ON HEART FUNCTION
M. Hobzova 1 , E. Sovova 2 , M. Sova 3 , K. Langova 4 , V. Kolek 1 . 1 Dept. of Pneumology, University Hospital Palacky University, Olomouc, Czech Republic; 2 I. Internal Dept., University Hospital Palacky University, Olomouc, Czech Republic; 3 Fac. of medicine and Dentistry, Palacky University, Olomouc, Czech Rep; 4 Dept. of Medical Biophysics, Palacky University, Olomouc, Czech Republic Objectives: The aim of the study was to evaluate the effects of CPAP treat-
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
there was an improvement in the domain of bodily pain. This finding could be explained by the association of OSAS with the inflammatory processes that cause pain, which can be reversed with treatment. Support: AFIP, FAPESP (2007/06232-0), CNPq
303
PERIPHERAL VASOCONSTRICTION AND NOCTURNAL BLOOD PRESSURE CONTROL IN HYPERTENSIVE SLEEP APNEA PATIENTS
D. Zou 1 , L. Grote 1 , D.N. Eder 1 , J. Radlinski 2 , Y. Peker 3 , J. Hedner 1 . 1 Sleep Laboratory, Department of Pulmonary Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 2 Department of Pathophysiology of Respiratory System, Institute for Tuberculosis and Lung Diseases Rabka-Zdrój Branch, Rabka-Zdrój, Poland; 3 Sleep Medicine Unit, Department of Neurology and Rehabilitation Medicine, Skaraborg Hospital, Skövde, Sweden Objective: Pulse wave attenuation that occurs in association with obstructive sleep apnea (OSA) is sympathetically mediated. Doxazosin (DO) is a peripheral α-receptor inhibitor, and Enalapril (EN) is an ACE inhibitor. The aim of this study was to compare the effects of DO and EN on digital vasoconstriction and nocturnal blood pressure (BP) control in hypertensive OSA patients. Methods: A double-blind crossover study on DO (4 mg/day for 2 weeks, followed by 8 mg/day for an additional 2 weeks) and EN (10 mg/day and 20 mg/day, respectively) was undertaken in 14 OSA patients with hypertension. The patients had a mean age of 55±7 years and a mean body mass index of 30.1±3.8 kg/m2 . The patient assessment, which was performed at the end of each treatment period, included ambulatory 24-hour BP, a full-night polysomnography with simultaneous peripheral arterial tonometry (PAT) and beat-to-beat finger BP monitoring (Finapres). Nighttime BP and digital vasoconstrictions, which are associated with apneic events and are measured by the PAT ratio, were analyzed. Results: There was no difference between the two treatments for either the 24-hour BP profile or the severity of OSA. There was, however, a significant difference between the DO and EN treatments with respect to the nighttime beat-to-beat finger BP (systolic BP 129±13 vs. 119±23 mmHg, P=0.02; diastolic BP 81±12 vs. 74±14 mmHg, P=0.04). In a linear mixed effects regression model, the PAT ratio increased 8.3% after treatment with DO compared to treatment with EN (P<0.0001). Each percentage of SaO2 desaturation and each second of apnea length were associated with a 0.7% and 0.3% decrease in the PAT ratio, respectively (P<0.0001). REM sleep was associated with a 2.7% increase in the PAT ratio in contrast to that of NREM sleep. Conclusion: Digital vasoconstriction that is associated with apneic events is α-receptor mediated. DO appear to have a proportionally worse effect on nocturnal BP control when compared with that of EN in hypertensive OSA patients.
Treatment Outcome Clinical Trial Research
304
A RANDOMIZED, DOUBLE-BLIND, 6-WEEK, DOSE-RANGING STUDY OF PREGABALIN IN SUBJECTS WITH RESTLESS LEGS SYNDROME
R. Allen 1 , C. Chen 2 , A. Soaita 2 , C. Wohlberg 3 , L. Knapp 2 , D. Garcia-Borreguero 4, J. Miceli 2 . 1 Johns Hopkins Department of Neurology, Baltimore, MD, USA; 2 Pfizer Global Research and Development, New London, CT, USA; 3 Pfizer Global Research and Development, New York, NY, USA; 4 Sleep Research Institute, University of Madrid, Madrid, Spain Introduction: Clinical data suggest pregabalin as a potential treatment for primary restless legs syndrome (RLS). Objectives: To characterize the dose-response relationship of pregabalin with respect to both efficacy and safety, in patients with idiopathic RLS. Methods: This was a 6-week, randomized, double-blind, placebo-controlled, dose-ranging study of pregabalin in adults with moderate to severe idiopathic RLS. Eligible patients were randomly assigned a fixed-dose pregabalin 50, 100, 150, 300, and 450 mg/day or a placebo. Assessments were conducted at baseline and in weeks 1, 2, 4, and 6. The primary endpoint was change from baseline to week 6 in the International Restless Legs Syndrome Scale
(IRLS) total score. Secondary endpoints included Clinical Global Impressions - Improvement Scale (CGI-I) responders, sleep assessments, other global and quality of life assessments and safety/tolerability. Results: A total of 137 patients participated in the study, randomly distributed into 6 similar-sized groups. At baseline, mean (SD) IRLS total scores for placebo, 50, 100, 150, 300, and 450 mg/day pregabalin groups were 23.8 (7.2), 24.6 (6.7), 25.3 (6.4), 26.2 (7.4), 25.0 (7.4), and 24.1 (7.8), respectively; the least square mean (SE; P value) differences in change from baseline to week 6 in IRLS total score (pregabalin vs. placebo) were -4.1 (2.5; P=0.0983), -4.0 (2.4; P=0.0966), -8.3 (2.5; P=0.0013), -5.2 (2.4; P=0.0353), and -8.5 (2.5; P=0.0006), respectively. From the dose-response analysis, a pregabalin dose of 123.9 mg/day was estimated to produce a 90% maximal effect in reducing RLS symptoms. Predicted mean changes from baseline to week 6 in IRLS scores using a dose response E-max model indicated that pregabalin doses of 100 to 450 mg/day corresponded to at least an average 13.6 point-reduction (at least an average 6-point placebo-corrected treatment difference). The percentage of CGI-I responders was numerically greater among patients who received pregabalin 300 or 450 mg/day compared with patients receiving placebo or lower doses of pregabalin at the last observation. The most common adverse events were dizziness, somnolence, fatigue, dry mouth and headache. Conclusions: This dose-ranging study showed that pregabalin reduced RLS symptoms in a dose-related manner with doses >150 mg/day providing significant symptom reduction. Pregabalin was safe and well tolerated across the entire dosing range. Support: Funded by Pfizer Inc.
305
EVALUATION OF A LOW-COST ORAL APPLIANCE: A PILOT STUDY
J.J. Cervo 1 , R.C. Langien 1 , S.C. Fagondes 2 , S.W. Samuel 1 , M.L. Grossi 3 , S.S. Menna Barreto 2 . 1 UFRGS; 2 HCPA; 3 PUCRS Introduction: Oral appliances (OA) are recommended for primary snoring and for patients with mild to moderate obstructive sleep apnea (OSA). They do have some advantages over CPAP treatment such as improved comfort and lower costs. OSA is an increasing public health problem, thus, concerns about the economical aspects of its treatment are very important, especially in Brazil, a developing country. The purpose of this study was to investigate the efficacy of a modified monobloc OA made with inexpensive materials for the treatment of patients with mild to moderate OSA, for further investigation. Methods: Five male patients with BMI less than 30 kg/m2 and an apnea/hypopnea index (AHI) less than 30 events/h according to the baseline polysomnography (PSG) were treated with a low-cost modified monobloc OA. They used the OA during a mean period of 86,8±4,21 nights. A second PSG was performed with patients using the OA. The following variables were evaluated: AHI, average oxygen saturation (SpO2), minimum SpO2 (nadir SpO2) and subjective daytime sleepiness evaluation (Epworth Sleepiness Scale). Results: The mean BMI was 28,6±0,39 kg/m2 and mean age was 51,8 years old (range 46 to 60 years old). PSG showed statistically significant mean reduction of 83,5%, from baseline AIH (11,26±4,12 events/h) to AHI with OA (2,31±2,23 events/h). Nadir SpO2 increased from 86±3,4 to 90,4±1,3, with a mean increase of 4,87%. The average SpO2 did not change for the two groups. There was a mean reduction of one point in the Epworth Sleepiness Scale (Signal Test, p<0,05). No clinical complication was noticed in any participant, on teeth or soft tissues. Conclusion: This easy assembly and low-cost modified model of OA improved the outcomes and presented no complications in a small group of OSA patients and may be an appropriate alternative to be used in a larger investigation.
306
THE INFLUENCE OF TREATMENT BY CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) ON HEART FUNCTION
M. Hobzova 1 , E. Sovova 2 , M. Sova 3 , K. Langova 4 , V. Kolek 1 . 1 Dept. of Pneumology, University Hospital Palacky University, Olomouc, Czech Republic; 2 I. Internal Dept., University Hospital Palacky University, Olomouc, Czech Republic; 3 Fac. of medicine and Dentistry, Palacky University, Olomouc, Czech Rep; 4 Dept. of Medical Biophysics, Palacky University, Olomouc, Czech Republic Objectives: The aim of the study was to evaluate the effects of CPAP treat-