Obstructive Sleep ApneaNCT00950495
Oral Appliance Therapy in Obstructive Sleep Apnea
A study testing Mandibular Advancement Device (MAD) and nasal CPAP in people with Obstructive Sleep Apnea, run by VU University of Amsterdam at 1 site in Netherlands.
Trial summary
The aim of the study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure(nCPAP) and of an intra-oral placebo device in obstructive sleep apnea (OSA) patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Mandibular Advancement Device (MAD) and nasal CPAP
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2003to Jul 2009
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age > 18 years
- apnea-hypopnea index (AHI) between 5 and 45 events per hour
Who cannot join
- evidence of respiratory/ sleep disorders other than obstructive sleep apnea
- a body mass index (BMI) > 40
- medication usage that could influence respiration or sleep
- periodic limb movement disorder
- previous treatment with CPAP or MAD
- reversible morphological upper airway abnormalities (e.g., enlarged tonsils)
Show all 10Show fewer
- temporomandibular disorders (based on a functional examination of the masticatory system)
- untreated periodontal problems
- dental pain
- lack of retention possibilities for a mandibular advancement device or a placebo appliance
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Centre for Dentistry Amsterdam (ACTA), Research Institute Move, University of Amsterdam and VU University Amsterdam
Amsterdam, 1066 EA
About this study
Official title: Effects of an Oral Appliance on Obstructive Sleep Apnea: A Randomized, Placebo-Controlled Trial
The aim of the study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure(nCPAP) and of an intra-oral placebo device in obstructive sleep apnea (OSA) patients. The hypothesis for this study was that both MAD therapy and nCPAP therapy have similar, better treatment effects than placebo therapy in OSA. The study was performed according to the CONSORT (consolidated standards of reporting trials) statement (Altman et al., 2001), employing a parallel-group, randomized, placebo-controlled trial design.
Read the detailed description
Setting and participants:
Eligible OSA patients, living in the greater Amsterdam area, were referred to the Slotervaart Medical Center by their family physician. All patients underwent a thorough medical examination, including a full polysomnographic (PSG) recording, at the departments of Neurology, Pulmonary Medicine, and ENT, as well as a thorough dental examination at the Department of Oral Kinesiology of ACTA. OSA patients were invited for participation in this study when they fulfilled the inclusion criteria and exclusion criteria.
Randomisation and allocation:
After written informed consent was obtained, the patients were randomly allocated to one of three therapy groups (MAD, nCPAP, or placebo; see below). To ensure that the groups were of approx. the same size, block randomisation was used. Block sizes were 6, 12, and 18; sizes were randomly varied. The allocation sequence was automatically generated and subsequently concealed by an independent co-worker, who kept a paper copy in a lockable drawer. Sealed opaque envelopes were used to conceal the allocation from the principal investigator.
Interventions and blinding:
Three forms of therapy interventions were used in this parallel-group study. First, an individually fabricated MAD with an adjustable protrusive mandibular position at a constant vertical dimension was used. Second, nCPAP of the REMstar Pro system was used (Respironics, Herrsching, Germany). Third, a thin (< 1 mm), hard acrylic-resin palatal splint with only a partial palatal coverage was used as a placebo.
Patients were blinded to the nature of the assigned therapy (placebo or active). After evaluating the therapy, all patients were asked if they were of the opinion that they had received an active or placebo treatment. Blinding of the analyst was ascertained by assigning codes to data sets and by analyzing these sets in random blocks.
Procedure:
From all patients, two full polysomnographic (PSG) recordings were obtained in the sleep laboratory of the Slotervaart Medical Center, using Siesta hardware and Pro-Fusion software (Compumedics, Abbotsford, Australia): one before therapy assignment (baseline PSG) and one after 6 ± 2 months (mean ± SD) of treatment (therapy evaluation PSG). For the MAD and nCPAP groups, the third and fourth PSG recordings for therapy evaluation were performed 6 months and one year after the first therapy evaluation (long-term follow-up). The primary and secondary outcome measures were obtained at baseline and at therapy evaluations.
The MAD and nCPAP were titrated before the start of the treatment. The titration of the nCPAP was performed during a third sleep laboratory examination. The pressure was increased in incremental steps of 1 cm H2O/h, until respiratory disturbances and respiration-related arousals were reduced to ≤ 5/h, and snoring was minimized.
For the titration of the MAD, four ambulatory PSG recordings were obtained at regular intervals, using Monet hardware and Rembrandt Software (Medcare Automation B.V., Amsterdam, The Netherlands). The most effective protrusion position of the MAD (i.e., the mandibular position that yielded the lowest AHI value) was chosen from among four randomly offered positions (viz., 0%, 25%, 50%, and 75% of the maximum protrusion).
For the placebo group, the study procedure was made equally intense as that for the MAD group by making four ambulatory PSG recordings at regular intervals as well.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Mandibular Advancement Device (MAD), nasal CPAP, placebo
- Keywords
- Parallel design, Oral appliance, Mandibular advancement device, Continuous positive airway pressure, Placebo, Therapy, Side-effects, Compliance
- Medical subject headings
- Sleep Apnea, Obstructive, Patient Compliance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mandibular Advancement Device (MAD)Device
Also called mandibular repositioning appliance, mandibular advancement appliance, mandibular repositioning device, mandibular repositioning splint
This oral appliance keeps the mandible and the tongue in a protruded position. This results in an upper respiratory tract widening and/or reduced collapsibility of the upper airway, thereby preventing the upper airway collapse during sleep.
nasal CPAPDevice
The CPAP machine delivers a stream of compressed air via a hose to a nose mask, splinting the airway (keeping it open under air pressure) so that unobstructed breathing becomes possible, reducing and/or preventing apneas and hypopneas
placeboDevice
as a placebo, a thin (< 1 mm), hard acrylic-resin palatal splint with only a partial palatal coverage was used
| Study group | Role | What they receive |
|---|---|---|
| Mandibular advancement device (MAD) | Active comparator | an MAD is placed in the mouth prior to sleep. After waking up in the morning, the appliance is removed. Receives: Device: Mandibular Advancement Device (MAD) |
| nasal CPAP | Active comparator | The device is turned on, and the nasal mask is placed on the nose prior to sleep. After waking up in the morning, the device is turned off and the mask is removed Receives: Device: nasal CPAP |
| placebo | Placebo comparator | the placebo appliance is placed in the mouth prior to sleep. After waking up in the morning, the appliance is removed. Receives: Device: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
apnea-hypopnea index (AHI)
Measured: 6 months
Secondary outcomes (1)
other respiratory variables (apnea-hypopnea index during different sleep stages and positions);sleep variables (sleep stages and arousals);excessive daytime sleepiness;health perception;compliance;snoring reports; side-effects
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2009 (estimated)
- Study startOct 2003
- Primary completionJan 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- VU University of Amsterdam
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ghizlane Aarab, VU University of Amsterdam
- Investigators
- Ghizlane Aarab, DDS, Principal investigator, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute Move, University of Amsterdam and VU University Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00950495
- Sponsor's protocol ID
- U/1731/0326
- Status last verified
- Dec 2014
- First submitted
- 30 Jul 2009
- Last updated
- 25 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Effects of an oral appliance with different mandibular protrusion positions at a constant vertical dimension on obstructive sleep apnea. Clin Oral Investig. 2010 Jun;14(3):339-45. doi: 10.1007/s00784-009-0298-9. Epub 2009 Jun 18.
PubMed 19536571Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Variability in the apnea-hypopnea index and its consequences for diagnosis and therapy evaluation. Respiration. 2009;77(1):32-7. doi: 10.1159/000167790. Epub 2008 Oct 29.
PubMed 18957843Aarab G, Lobbezoo F, Wicks DJ, Hamburger HL, Naeije M. Short-term effects of a mandibular advancement device on obstructive sleep apnoea: an open-label pilot trial. J Oral Rehabil. 2005 Aug;32(8):564-70. doi: 10.1111/j.1365-2842.2005.01467.x.
PubMed 16011634Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial. Respiration. 2011;81(5):411-9. doi: 10.1159/000319595. Epub 2010 Oct 20.
PubMed 20962502Aarab G, Lobbezoo F, Heymans MW, Hamburger HL, Naeije M. Long-term follow-up of a randomized controlled trial of oral appliance therapy in obstructive sleep apnea. Respiration. 2011;82(2):162-8. doi: 10.1159/000324580. Epub 2011 Mar 31.
PubMed 21454959Nikolopoulou M, Naeije M, Aarab G, Hamburger HL, Visscher CM, Lobbezoo F. The effect of raising the bite without mandibular protrusion on obstructive sleep apnoea. J Oral Rehabil. 2011 Sep;38(9):643-7. doi: 10.1111/j.1365-2842.2011.02221.x. Epub 2011 Apr 5.
PubMed 21463349
Study at a glance
From the registry record, last updated by the sponsor on 25 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of an Oral Appliance on Obstructive Sleep Apnea: A Randomized, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT00950495
- Acronym / sponsor ID
- U/1731/0326
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Parallel design, Oral appliance, Mandibular advancement device, Continuous positive airway pressure, Placebo, Therapy, Side-effects, Compliance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- VU University of AmsterdamUniversity, hospital or other
- Study start
- Oct 2003
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 31 Jul 2009 (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.
The aim of the study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure(nCPAP) and of an intra-oral placebo device in obstructive sleep apnea (OSA) patients. The hypothesis for this study was that both MAD therapy and nCPAP therapy have similar, better treatment effects than placebo therapy in OSA. The study was performed according to the CONSORT (consolidated standards of reporting trials) statement (Altman et al., 2001), employing a parallel-group, randomized, placebo-controlled trial design.
Detailed description
Setting and participants:
Eligible OSA patients, living in the greater Amsterdam area, were referred to the Slotervaart Medical Center by their family physician. All patients underwent a thorough medical examination, including a full polysomnographic (PSG) recording, at the departments of Neurology, Pulmonary Medicine, and ENT, as well as a thorough dental examination at the Department of Oral Kinesiology of ACTA. OSA patients were invited for participation in this study when they fulfilled the inclusion criteria and exclusion criteria.
Randomisation and allocation:
After written informed consent was obtained, the patients were randomly allocated to one of three therapy groups (MAD, nCPAP, or placebo; see below). To ensure that the groups were of approx. the same size, block randomisation was used. Block sizes were 6, 12, and 18; sizes were randomly varied. The allocation sequence was automatically generated and subsequently concealed by an independent co-worker, who kept a paper copy in a lockable drawer. Sealed opaque envelopes were used to conceal the allocation from the principal investigator.
Interventions and blinding:
Three forms of therapy interventions were used in this parallel-group study. First, an individually fabricated MAD with an adjustable protrusive mandibular position at a constant vertical dimension was used. Second, nCPAP of the REMstar Pro system was used (Respironics, Herrsching, Germany). Third, a thin (< 1 mm), hard acrylic-resin palatal splint with only a partial palatal coverage was used as a placebo.
Patients were blinded to the nature of the assigned therapy (placebo or active). After evaluating the therapy, all patients were asked if they were of the opinion that they had received an active or placebo treatment. Blinding of the analyst was ascertained by assigning codes to data sets and by analyzing these sets in random blocks.
Procedure:
From all patients, two full polysomnographic (PSG) recordings were obtained in the sleep laboratory of the Slotervaart Medical Center, using Siesta hardware and Pro-Fusion software (Compumedics, Abbotsford, Australia): one before therapy assignment (baseline PSG) and one after 6 ± 2 months (mean ± SD) of treatment (therapy evaluation PSG). For the MAD and nCPAP groups, the third and fourth PSG recordings for therapy evaluation were performed 6 months and one year after the first therapy evaluation (long-term follow-up). The primary and secondary outcome measures were obtained at baseline and at therapy evaluations.
The MAD and nCPAP were titrated before the start of the treatment. The titration of the nCPAP was performed during a third sleep laboratory examination. The pressure was increased in incremental steps of 1 cm H2O/h, until respiratory disturbances and respiration-related arousals were reduced to ≤ 5/h, and snoring was minimized.
For the titration of the MAD, four ambulatory PSG recordings were obtained at regular intervals, using Monet hardware and Rembrandt Software (Medcare Automation B.V., Amsterdam, The Netherlands). The most effective protrusion position of the MAD (i.e., the mandibular position that yielded the lowest AHI value) was chosen from among four randomly offered positions (viz., 0%, 25%, 50%, and 75% of the maximum protrusion).
For the placebo group, the study procedure was made equally intense as that for the MAD group by making four ambulatory PSG recordings at regular intervals as well.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mandibular advancement device (MAD) | Active comparator | Device: Mandibular Advancement Device (MAD)an MAD is placed in the mouth prior to sleep. After waking up in the morning, the appliance is removed. |
| nasal CPAP | Active comparator | Device: nasal CPAPThe device is turned on, and the nasal mask is placed on the nose prior to sleep. After waking up in the morning, the device is turned off and the mask is removed |
| placebo | Placebo comparator | Device: placebothe placebo appliance is placed in the mouth prior to sleep. After waking up in the morning, the appliance is removed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- age > 18 years
- apnea-hypopnea index (AHI) between 5 and 45 events per hour
Key exclusion criteria (10 listed)
- evidence of respiratory/ sleep disorders other than obstructive sleep apnea
- a body mass index (BMI) > 40
- medication usage that could influence respiration or sleep
- periodic limb movement disorder
- previous treatment with CPAP or MAD
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 |
|---|---|---|
| Mandibular Advancement Device (MAD)Also: mandibular repositioning appliance, mandibular advancement appliance, mandibular repositioning device, mandibular repositioning splintThis oral appliance keeps the mandible and the tongue in a protruded position. This results in an upper respiratory tract widening and/or reduced collapsibility of the upper airway, thereby preventing the upper airway collapse during sleep. | Device | Mandibular advancement device (MAD) |
| nasal CPAPThe CPAP machine delivers a stream of compressed air via a hose to a nose mask, splinting the airway (keeping it open under air pressure) so that unobstructed breathing becomes possible, reducing and/or preventing apneas and hypopneas | Device | nasal CPAP |
| placeboas a placebo, a thin (< 1 mm), hard acrylic-resin palatal splint with only a partial palatal coverage was used | Device | placebo |
Primary outcome
apnea-hypopnea index (AHI)
Time frame: 6 months
1 secondary outcome
other respiratory variables (apnea-hypopnea index during different sleep stages and positions);sleep variables (sleep stages and arousals);excessive daytime sleepiness;health perception;compliance;snoring reports; side-effects
Time frame: 6 months
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 25 Dec 2014.
- Results publication: PubMed 19536571Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Effects of an oral appliance with different mandibular protrusion positions at a constant vertical dimension on obstructive sleep apnea. Clin Oral Investig. 2010 Jun;14(3):339-45. doi: 10.1007/s00784-009-0298-9. Epub 2009 Jun 18.
- Results publication: PubMed 18957843Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Variability in the apnea-hypopnea index and its consequences for diagnosis and therapy evaluation. Respiration. 2009;77(1):32-7. doi: 10.1159/000167790. Epub 2008 Oct 29.
- Results publication: PubMed 16011634Aarab G, Lobbezoo F, Wicks DJ, Hamburger HL, Naeije M. Short-term effects of a mandibular advancement device on obstructive sleep apnoea: an open-label pilot trial. J Oral Rehabil. 2005 Aug;32(8):564-70. doi: 10.1111/j.1365-2842.2005.01467.x.
- Results publication: PubMed 20962502Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial. Respiration. 2011;81(5):411-9. doi: 10.1159/000319595. Epub 2010 Oct 20.
- Results publication: PubMed 21454959Aarab G, Lobbezoo F, Heymans MW, Hamburger HL, Naeije M. Long-term follow-up of a randomized controlled trial of oral appliance therapy in obstructive sleep apnea. Respiration. 2011;82(2):162-8. doi: 10.1159/000324580. Epub 2011 Mar 31.
- Results publication: PubMed 21463349Nikolopoulou M, Naeije M, Aarab G, Hamburger HL, Visscher CM, Lobbezoo F. The effect of raising the bite without mandibular protrusion on obstructive sleep apnoea. J Oral Rehabil. 2011 Sep;38(9):643-7. doi: 10.1111/j.1365-2842.2011.02221.x. Epub 2011 Apr 5.
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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.
Ghizlane Aarab, DDS principal investigator
Academic Centre for Dentistry Amsterdam (ACTA), Research Institute Move, University of Amsterdam and VU University Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mandibular Advancement Device (MAD) and nasal CPAP in people with Obstructive Sleep Apnea, run by VU University of Amsterdam at 1 site in Netherlands.
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 2 inclusion and 10 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 25 Dec 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 Netherlands. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
apnea-hypopnea index (AHI) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00950495, which also lists 6 linked publications.
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 25 Dec 2014.