The objective is to explore the efficacy of pharmacological weight reduction compared with CPAP treatment in patients with moderate to severe obstructive sleep apnea (OSA). MedDRA version: 12.0 Level: LLT Classification code 10055577 Term: Obstructive sleep apnea syndrome
Conditions
Interventions
Trade Name: Zonegran
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ZONISAMIDE
CAS Number: 68291-97-4
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 100-3
Sponsors
The Sahlgrenska Academy, University of Gothenburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Males/females 18 to 75 years 3. An Apnea-Hypopnea Index (AHI)>15 and an Epworth Sleepiness Scale score (ESS)>6 4. Body mass index (BMI) between >27 and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity to sulfonamides or zonisamide. 2. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity 3. Subjects with a seizure disorder 4. Clinically significant renal (serum creatinine >2.0 mg/dL or >130 ?mol/L), neurological, metabolic (e.g. Type 1 or 2 diabetes), haematological or hepatic disease (ASAT or ALAT >2 times the upper limit of normal). 5. Subjects who have taken any weight loss medications (prescription or over-the-counter) within one month prior to Enrollment 6. Subjects with occupations designated as high risk or safety sensitive including patients who have to handle complex machinery or are professional drivers where there may be an increased risk for work or traffic accidents. 7. Unstable angina pectoris, unstable hypertension (diastolic blood pressure above 100 on treatment for more than 3 months), diabetes (fasting plasma glucose above 7 mmoles/l) 8. Uncontrolled congestive heart failure 9. Myocardial infarction or coronary vessel intervention within the previous 6 months period 10. Subjects with uncontrolled hypertension (defined as a diastolic blood pressure ?100 mmHg and/or a systolic blood pressure =180 mmHg with or without medication). Hypertensive subjects on medications must have been on the same dose of the same antihypertensive medication for at least two months prior to Enrollment. 11. Previously diagnosed or treated clinically significant cardiac arrhythmia 12. Clinically significant chronic pulmonary or gastrointestinal disease 13. Clinical history of depression as judged by the investigator or other previous or present clinically significant psychiatric disease 14. Pregnancy or lactation. Women of childbearing potential should use effective birth control prior to and during the study 15. Suspected or confirmed poor compliance 16. Alcohol or drug abuse during the last year 17. Subjects with any other significant condition that, in the opinion of the investigator, could interfere with participation in the study. 18. Severe nocturnal hypoxia defined as more than 10 episodes with an oxygen desaturation exceeding 50% or signs of lacking resaturation between desaturations on previous recordings according to investigators judgement. 19. Participation in another clinical study during the last 6 months 20. Inability to understand and complete the questionnaires
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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) using calculated effective change in AHI score as the primary variable. The effect will be expressed in terms of apnea alleviation after zonisamide or CPAP;Secondary Objective: The secondary objective is to investigate the direct effect of zonisamide vs. placebo on sleep disordered breathing (AHI score) after short-term (4 weeks) treatment. Other secondary objectives include the effect on other markers of sleep apnea like 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 after short- and long-term treatment. ;Primary end point(s): The primary endpoint will be expressed in terms of apnea alleviation after zonisamide or CPAP. Calculated and estimated measures of sleep apnea reduction: •Apnea/hypopnea alleviation which describes the total calculated number of apneas/hypopneas on treatment. In nCPAP treated patients alleviation is calculated after adjustment for treatment efficacy and user time (CPAP meter reader). •User time is adjusted for habitual number of sleep hours (sleep diary). •In the drug treatment group apnea/hypopnea alleviation is expressed as remaining AHI after treatment (PSG recording at 6 months) assuming that weight reduction/direct effect reached provides a similar effect on sleep apnea for every night and each hour slept (This measure is related to loss of body weight and hence independent of absolute compliance with drug unless there is a significant direct effect of the drug treatment). | — |
Countries
Sweden
Outcome results
None listed