Sleep ApneaPhase 2NCT01765608
Zonisamide for the Treatment of Obstructive Sleep Apnea in Overweight/Obese Patients
A Phase 2 study testing Zonisamide and nCPAP in people with Sleep Apnea and Obstructive Sleep Apnea, run by Göteborg University at 1 site in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sleep Apnea, Obstructive Sleep Apnea, Obesity
- What is being tested?
- Zonisamide and nCPAP
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteSweden
- Study dates
- Mar 2010to Jun 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Center for Sleep and Vigilance Disorders
Gothenburg, Västra Götaland County, 40530
About this study
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.
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.
- Conditions
- Sleep Apnea, Obstructive Sleep Apnea, Obesity
- Being tested
- Zonisamide, Placebo, nCPAP
- 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
- Medical subject headings
- Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Obesity, Apnea, Respiration Disorders, Sleep Wake Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZonisamideDrug
Also called Zonegran®
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.
PlaceboDrug
nCPAPDevice
Also called nCPAP - Nasal Continuous Positive Airway Pressure., ResMed - S9 AutoSet™, ResMed - S8 AutoSet Spirit™ II
| Study group | Role | What they receive |
|---|---|---|
| Zonisamide | Experimental | 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. Receives: Drug: Zonisamide |
| Placebo | Active comparator | 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. Receives: Drug: Placebo |
| nCPAP | Active comparator | 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. Receives: Device: nCPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: Baseline to 4 weeks.
Secondary outcomes (2)
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.
Measured: baseline to 24 weeks
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).
Measured: Baseline to 4 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study startMar 2010
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep ApneaStudies of the same condition, open and under way.
- More trials run by Göteborg UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Göteborg University
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Jan Hedner, MD. Prof., Principal investigator, Department of Internal Medicine. Center for Sleep and Vigilance Disorders
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765608
- Sponsor's protocol ID
- ZON-01
- Other IDs
- 2009-015859-24, 2009
- Status last verified
- Feb 2014
- First submitted
- 8 Jan 2013
- Last updated
- 20 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01765608
- Acronym / sponsor ID
- ZON-01
- Conditions
- Sleep Apnea, Obstructive Sleep Apnea, Obesity
- Keywords
- Zonisamide, Zonegran, Obstructive Sleep apnea, Apnea, Respiration Disorders, Sleep Disorders, Obesity, Anti-Obesity Agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Göteborg UniversityUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- Mar 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 10 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Zonisamide | Experimental | Drug: ZonisamideZonisamide (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. |
| Placebo | Active comparator | Drug: PlaceboMatched 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. |
| nCPAP | Active comparator | Device: nCPAPContinuous 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZonisamideAlso: Zonegran®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. | Drug | Zonisamide |
| Placebo | Drug | Placebo |
| nCPAPAlso: nCPAP - Nasal Continuous Positive Airway Pressure., ResMed - S9 AutoSet™, ResMed - S8 AutoSet Spirit™ II | Device | nCPAP |
Primary outcome
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 .
2 secondary outcomes
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
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Hedner, MD. Prof. principal investigator
Department of Internal Medicine. Center for Sleep and Vigilance Disorders
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zonisamide and nCPAP in people with Sleep Apnea and Obstructive Sleep Apnea, run by Göteborg University at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2014; AzTrials last refreshed its copy on 8 Nov 2026.