Epilepsy, Obstructive Sleep Apnea, Sleep Apnea
Conditions
Keywords
epilepsy, sleep apnea, obstructive sleep apnea, continuous positive airway pressure, CPAP
Brief summary
The purpose of this trial is to work out design issues prior to conducting a definitive phase 3 trial to determine whether treating sleep-related breathing disorders in people with epilepsy results in improvement in seizure control or an improvement in alertness during the day.
Detailed description
Despite appropriate treatment with medications, individuals with epilepsy often continue to have seizures, and many suffer from excessive daytime sleepiness and poor quality of life. Evidence from case studies suggests that treatment of coexisting obstructive sleep apnea (OSA)-stoppage in breathing during sleep-can reduce the frequency of seizures in people with epilepsy that is resistant to antiepileptic medication. In this study, individuals with symptoms of OSA and 2 or more seizures a month who meet study criteria will undergo polysomnography, a test that continuously monitors normal and abnormal physiological activity during sleep. Those individuals who test positive for OSA will be randomized to either therapeutic or placebo continuous positive airway pressure (CPAP)-a mask treatment for sleep apnea-for 10 weeks, during which time seizure frequency, daytime sleepiness, health-related quality of life, and CPAP compliance will be assessed.
Interventions
DEVICEcontinuous positive airway pressure (CPAP)
a mask treatment for sleep apnea
DEVICEPlacebo-CPAP
Placebo-CPAP
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of 18 years or older. * A history supportive of obstructive sleep apnea. * Subject is able and willing to provide informed consent and to cooperate with polysomnography. * Four or more quantifiable seizures per month. * Subjects and their physicians agree to have their medication regimens optimized so that they are on the best regimen titrated to therapeutic benefit prior to the baseline phase of the study.
Exclusion criteria
* Seizures secondary to drugs, alcohol, infection, neoplasia, demyelination, metabolic illness, or progressive degenerative disease. * Non-epileptic spells (e.g., pseudoseizures) alone or in combination with epileptic seizures. * Narcolepsy or another primary sleep disorder that requires intervention with medications and which may affect results of study (e.g., severe periodic limb movement disorder). * Effectively treated OSA or prior exposure to continuous positive airway pressure. * History of poor compliance with antiepileptic medications. * Current treatment with the vagus nerve stimulator. * Pregnancy. * A significant history of medical or psychiatric disease which may impair participation in the trial. * A history of alcohol or drug abuse during the one-year period prior to trial participation. * Evidence of medical instability (e.g., congestive heart failure, cardiac arrhythmias, pulmonary disease) due to obstructive sleep apnea. * Subjects who are unaware of the majority of their seizures and lack a reliable witness. * Greater than ten seizures a day.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CPAP Adherence/Tolerance as Measured by Proportion of Nights Used | 10 weeks | This measure quantifies how well patients use their CPAP. The standard unit of measurement is proportion of nights that the CPAP is used by a participant (total nights used/total nights the device could have been used), averaged across all participants . Data were downloaded by a card placed in the CPAP machine reflecting use over the entire 10 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients That Were Able to be Blinded to CPAP or Placebo CPAP | 10 weeks | Patients all received a CPAP machine which either delivered CPAP or provided the patient with placebo CPAP, which had the same sensation as receiving CPAP |
| Number of Patients Requiring Only One Night of Baseline Sleep Study to Detect Sleep Apnea | prior to randomization | The data presented below represent the number of participants who required only one night of baseline sleep study prior to randomization |
Countries
United States
Participant flow
Recruitment details
This pilot clinical trial was conducted between September 2002 and July 2005 at University of Michigan, Cleveland Clinic, University of North Carolina at Chapel Hill, and Vanderbilt University, with a Data Coordinating Center at the University of Michigan. 68 participants were enrolled and 35 were randomized.
Pre-assignment details
Epilepsy clinic patients initially meeting trial eligibility on the basis of chart review completed a validated instrument that assesses the likelihood of having obstructive sleep apnea, and underwent a sleep and epilepsy evaluation by the site investigator. 68 patients consented, 33 not randomized due to not meeting criteria or declined.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Continuous Positive Airway Pressure With placebo continuous positive airway pressure, the subject feels like he/she is receiving the real treatment because of the presence of a blower and mask. However, there is a large leak that prevents the subject from receiving adequate pressurized air to keep the airway open. | 13 |
| Continuous Positive Airway Pressure Continuous positive airway pressure is a standard treatment for obstructive sleep apnea that uses pressurized air delivered through a mask to keep the airway open and prevent obstruction during sleep. | 22 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Continuous Positive Airway Pressure | Placebo Continuous Positive Airway Pressure | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 13 Participants | 35 Participants |
| Age, Continuous | 42.7 years STANDARD_DEVIATION 12.3 | 40.2 years STANDARD_DEVIATION 14.3 | 41.8 years STANDARD_DEVIATION 12.9 |
| Region of Enrollment United States | 22 participants | 13 participants | 35 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 5 / 22 |
| serious Total, serious adverse events | 0 / 13 | 0 / 22 |
Outcome results
Primary
CPAP Adherence/Tolerance as Measured by Proportion of Nights Used
This measure quantifies how well patients use their CPAP. The standard unit of measurement is proportion of nights that the CPAP is used by a participant (total nights used/total nights the device could have been used), averaged across all participants . Data were downloaded by a card placed in the CPAP machine reflecting use over the entire 10 weeks.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Continuous Positive Airway Pressure | CPAP Adherence/Tolerance as Measured by Proportion of Nights Used | 0.74 proportion of nights used (total nights | Standard Deviation 0.24 |
| Continuous Positive Airway Pressure | CPAP Adherence/Tolerance as Measured by Proportion of Nights Used | 0.66 proportion of nights used (total nights | Standard Deviation 0.3 |
Comparison: The null hypothesis was that the groups would be similar in tolerance. This was a pilot study so we did not do a power calculation.p-value: 0.26Wilcoxon (Mann-Whitney)
Secondary
Number of Patients Requiring Only One Night of Baseline Sleep Study to Detect Sleep Apnea
The data presented below represent the number of participants who required only one night of baseline sleep study prior to randomization
Time frame: prior to randomization
Population: These are participants that were enrolled and assessed to determine if one night of baseline sleep study was sufficient to detect sleep apnea. This occurred prior to randomization. Five of the assessed participants were not randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Continuous Positive Airway Pressure | Number of Patients Requiring Only One Night of Baseline Sleep Study to Detect Sleep Apnea | 39 Participants |
Secondary
Number of Patients That Were Able to be Blinded to CPAP or Placebo CPAP
Patients all received a CPAP machine which either delivered CPAP or provided the patient with placebo CPAP, which had the same sensation as receiving CPAP
Time frame: 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Continuous Positive Airway Pressure | Number of Patients That Were Able to be Blinded to CPAP or Placebo CPAP | 22 participants |
| Continuous Positive Airway Pressure | Number of Patients That Were Able to be Blinded to CPAP or Placebo CPAP | 13 participants |