Obesity, Obstructive Sleep Apnea, Sleep Apnea
Conditions
Keywords
Zonisamide, Zonegran, Obstructive Sleep apnea, Apnea, Respiration Disorders, Sleep Disorders, Obesity, Anti-Obesity Agents, Carbonic Anhydrase, Carbonic Anhydrase Inhibitors, Enzyme Inhibitors, Sulfonamides, Therapeutic Uses, Pharmacologic Actions
Brief summary
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. Study hypothesis: 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.
Interventions
DRUGZonisamide
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.
DRUGPlacebo
DEVICEnCPAP
Sponsors
Eisai Inc.
Göteborg University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Males/females 18 to 75 years * An Apnea-Hypopnea Index (AHI)\>15 * Epworth Sleepiness Scale score (ESS)\>6 * Body mass index (BMI) between \>27 and \<35 kg/m2 (mild to moderate) * Clinically normal physical findings and laboratory values, as judged by the investigator
Exclusion criteria
* Hypersensitivity to sulfonamides or zonisamide. * History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity * Subjects with a seizure disorder * Clinically significant renal (serum creatinine \>2.0 mg/dL or \>130 µmol/L), neurological, metabolic (e.g. Type 1 or 2 diabetes), haematological or hepatic disease (ASAT or ALAT \>2 times the upper limit of normal). * Subjects who have taken any weight loss medications (prescription or over-the-counter) within one month prior to Enrollment * 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. * 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) * Uncontrolled congestive heart failure * Myocardial infarction or coronary vessel intervention within the previous 6 months period * 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. * Previously diagnosed or treated clinically significant cardiac arrhythmia * Clinically significant chronic pulmonary or gastrointestinal disease * Clinical history of depression as judged by the investigator or other previous or present clinically significant psychiatric disease * Pregnancy or lactation. Women of childbearing potential should use effective birth control prior to and during the study * Suspected or confirmed poor compliance * Alcohol or drug abuse during the last year * Subjects with any other significant condition that, in the opinion of the investigator, could interfere with participation in the study. * 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. * Participation in another clinical study during the last 6 months * Inability to understand and complete the questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary objective is to investigate the effect of zonisamide vs. placebo on sleep disordered breathing after short-term (4 weeks) treatment. | 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. | 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). |
Countries
Sweden
Outcome results
None listed