search
Back to results

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

Primary Purpose

Sleep Apnea, Obstructive Sleep Apnea, Obesity

Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Zonisamide
Placebo
nCPAP
Sponsored by
Göteborg University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea focused on measuring 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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Center for Sleep and Vigilance Disorders

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Zonisamide

Placebo

nCPAP

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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 .

Secondary Outcome Measures

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.
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).

Full Information

First Posted
January 8, 2013
Last Updated
February 19, 2014
Sponsor
Göteborg University
Collaborators
Eisai Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01765608
Brief Title
Zonisamide for the Treatment of Obstructive Sleep Apnea in Overweight/Obese Patients
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Göteborg University
Collaborators
Eisai Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea, Obstructive Sleep Apnea, Obesity
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zonisamide
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
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.
Arm Title
nCPAP
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Zonisamide
Other Intervention Name(s)
Zonegran®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Device
Intervention Name(s)
nCPAP
Other Intervention Name(s)
nCPAP - Nasal Continuous Positive Airway Pressure., ResMed - S9 AutoSet™, ResMed - S8 AutoSet Spirit™ II
Primary Outcome Measure Information:
Title
Primary objective is to investigate the effect of zonisamide vs. placebo on sleep disordered breathing after short-term (4 weeks) treatment.
Description
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 .
Time Frame
Baseline to 4 weeks.
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
baseline to 24 weeks
Title
Secondary objective is to investigate the effect of zonisamide vs. placebo on other sleep disordered breathing parameters after short-term (4 weeks) treatment.
Description
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).
Time Frame
Baseline to 4 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan Hedner, MD. Prof.
Organizational Affiliation
Department of Internal Medicine. Center for Sleep and Vigilance Disorders
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Sleep and Vigilance Disorders
City
Gothenburg
State/Province
Västra Götaland
ZIP/Postal Code
40530
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs