Zonisamide for the Treatment of Obstructive Sleep Apnea in Overweight/Obese Patients
This RCT explores the efficacy of Zonisamide (Zonegran®)on overweight/obese in patients with moderate to severe obstructive sleep apnea. Patients will be randomized to receive zonisamide, placebo or nasal continuous positive airway pressure (nCPAP) during 4 weeks. A 5 month open extension part will follow when patients in the tablet groups will all receive zonisamide. Patients in the open CPAP group will continue with CPAP treatment.
Controlled pharmacological weight reduction with Zonisamide will result in elimination of OSA and OSA sequels more effectively than nCPAP due to incomplete compliance with the mechanical treatment and a lack of direct beneficial metabolic effects after nCPAP. Further it is hypothesized that zonisamide has a direct pharmacological effect on respiratory control during sleep by its carbonic anhydrase inhibitory effects and this will result in a reduction of sleep disordered breathing.
|Sleep Apnea Obstructive Sleep Apnea Obesity||Drug: Zonisamide Drug: Placebo Device: nCPAP||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A 1 Month Randomized Placebo Controlled, Double Blind Trial With a 5 Month Open Extension Phase to Explore the Efficacy of Zonisamide on Apnea/Hypopnea Index in Overweight/Obese Sleep Apnea Patients.|
- Primary objective is to investigate the effect of zonisamide vs. placebo on sleep disordered breathing after short-term (4 weeks) treatment. [ Time Frame: Baseline to 4 weeks. ]The primary objective of this study is to explore the efficacy of pharmacological weight reduction on obstructive sleep apnea (OSA) by assessment of apnoea/hypopnea index (AHI) and oxygen desaturation index (ODI) 4 weeks .
- Longterm efficacy and effect of zonisamide on obstructive sleep apnea (OSA)in comparison to CPAP by assessment of apnoea/hypopnea index (AHI) after 24 weeks. [ Time Frame: baseline to 24 weeks ]The effect of CPAP will be expressed in terms of apnea alleviation. Other secondary objectives include the effect on oxygen desaturation, mean overnight oxygenation, sleep quality (by polysomnographic assessment), daytime sleepiness, daytime cognitive function, patient-reported outcomes, blood pressure and effects on metabolic markers.
- Secondary objective is to investigate the effect of zonisamide vs. placebo on other sleep disordered breathing parameters after short-term (4 weeks) treatment. [ Time Frame: Baseline to 4 weeks. ]Secondary objectives include the effect on other markers of sleep apnea like mean overnight oxygenation, sleep quality (by polysomnographic assessment), daytime sleepiness, daytime cognitive function, patient-reported outcomes, blood pressure and effects on metabolic markers after short term treatment (4 weeks).
|Study Start Date:||March 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Zonisamide (Zonegran®) 300 mg. Hard white capsule. The total length of zonisamide treatment will be 20 and 24 weeks ± 2 weeks including one or two 4 week titration phases in the placebo and zonisamide groups respectively. Dosing will be down titrated after finished study during 2-3 weeks.The maximum dose after titration will be administrated once daily. Evening medication should be taken 2 hours before bedtime. The tablets will be swallowed with 200 ml of water (room temperature) in an upright body position.
Zonisamide (Zonegran®) tablets will be administered according to a forced stepwise weekly titration scheme with weekly 100 mg escalations from 100 to 300 mg daily according to the manufacturer Eisai Inc.
Other Name: Zonegran®
Active Comparator: Placebo
Matched for Zonisamide. Hard white capsule. Manufactured by Eisai Inc. Placebo tablets will be administered according to a forced stepwise weekly titration scheme with weekly 1 tablet escalations from 1 to 3 tablets daily matching the Zonisamide (Zonegran ®) dosing regimen for a total duration of 4 weeks. Evening medication should be taken 2 hours before bedtime. The tablets will be swallowed with 200 ml of water (room temperature) in an upright body position.
Active Comparator: nCPAP
Continuous positive nasal airway pressure (nCPAP) delivers slightly pressurized air throughout the breathing cycle and will be given through a mask that is placed and secured over the person's nose. nCPAP titration will follow clinical routines whereby the patient is equipped with an autotitrating device (Sullivan S8 or S9). The standard setting is a pressure delivery in the pressure range 5-15 mbar and the full treatment is maintained in the patient´s home. The adequate performance of the device is controlled by user time readers and built-in memory cards and control readings are routinely performed within the first 4 weeks of treatment initiation. Patients will be encouraged via telephone calls for maximum use. Total duration of CPAP treatment is 24 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765608
|Center for Sleep and Vigilance Disorders|
|Gothenburg, Västra Götaland, Sweden, 40530|
|Principal Investigator:||Jan Hedner, MD. Prof.||Department of Internal Medicine. Center for Sleep and Vigilance Disorders|