Sleep Apnea, Obstructive
Conditions
Brief summary
In this protocol the investigators will test the effect of dalfampridine (a potassium channel blocker) on genioglossus muscle activity (EMG GG) during wakefulness and sleep in healthy control subjects.
Detailed description
Two overnight sleep studies, a placebo night and a drug night, will be performed approximately one week apart in random order. The placebo or drug will be administered 3 hours before lights out. At least 10 minutes of quiet wakefulness will be recorded to quantify the subject's awake EMG GG activity before the administration of placebo/dalfampridine. EMG GG activity will be measured again 10 mins before lights off and during stable NREM and REM sleep (free of arousals and other artifacts). During the second part of the night, the subjects will be connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which can provide a wide range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure and measure change in EMG GG as a function of epiglottic pressure (muscle responsiveness).
Interventions
DRUGPlacebo
Placebo 3 hrs before sleep
DRUGDalfampridine
Dalfampridine 10 mg extended release 3 hrs before sleep
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy control subjects
Exclusion criteria
* Cardiovascular disease other than well controlled hypertension * History of seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). | 1 night | The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O) | 1 night | Effect of dalfampridine on genioglossus muscle responsiveness to increased epiglottic pressure swings during sleep in healthy controls during NREM sleep. The variation of EMG GG is expressed here as % of maximal activation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Analyzed Participants All participants who were randomized, completed both study nights, and were included in the analysis. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | All Analyzed Participants |
|---|---|
| Age, Continuous | 28 years |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration).
The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns).
Time frame: 1 night
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). | Tonic genioglossus activity during sleep | 166 percentage of wakefulness value |
| Placebo | Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). | Phasic genioglossus activity during sleep | 245 percentage of wakefulness value |
| Dalfampridine | Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). | Tonic genioglossus activity during sleep | 136 percentage of wakefulness value |
| Dalfampridine | Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). | Phasic genioglossus activity during sleep | 163 percentage of wakefulness value |
Comparison: tonicp-value: 0.85Wilcoxon (Mann-Whitney)
Comparison: Phasic activityp-value: 0.322Wilcoxon (Mann-Whitney)
Secondary
Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O)
Effect of dalfampridine on genioglossus muscle responsiveness to increased epiglottic pressure swings during sleep in healthy controls during NREM sleep. The variation of EMG GG is expressed here as % of maximal activation.
Time frame: 1 night
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O) | -0.23 %max/cmH2O |
| Dalfampridine | Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O) | -0.36 %max/cmH2O |
p-value: 0.42Wilcoxon (Mann-Whitney)