Zonisamide for the Treatment of Obstructive Sleep Apnea in Overweight/Obese Patients

Obesity Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01765608
• Other study ID #: ZON-01
• Secondary ID: 2009-015859-24
• Status: Completed
• Phase: Phase 2
• First received: January 8, 2013
• Last updated: February 19, 2014
• Start date: March 2010
• Est. completion date: June 2013

Study information

• Verified date: February 2014
• Source: Göteborg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Obesity
• Obstructive Sleep Apnea
• Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Zonisamide
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.
• Placebo

Device:
• nCPAP

Locations

Country	Name	City	State
Sweden	Center for Sleep and Vigilance Disorders	Gothenburg	Västra Götaland

Sponsors (2)

Lead Sponsor	Collaborator
Göteborg University	Eisai Inc.

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary objective is to investigate the effect of zonisamide vs. placebo on sleep disordered breathing after short-term (4 weeks) treatment.	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 .	Baseline to 4 weeks.	Yes
Secondary	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.	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.	baseline to 24 weeks	Yes
Secondary	Secondary objective is to investigate the effect of zonisamide vs. placebo on other sleep disordered breathing parameters after short-term (4 weeks) treatment.	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).	Baseline to 4 weeks.	Yes