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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Dalfampridine | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo 3 hrs before sleep |
| |
| Dalfampridine |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 1 night |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 1 night |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sleep Disorders Research Program Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28387543 | Derived | Taranto-Montemurro L, Sands SA, Azarbarzin A, Marques M, de Melo CM, Edwards BA, Eckert DJ, Messineo L, White DP, Wellman A. Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults. Ann Am Thorac Soc. 2017 Jul;14(7):1177-1183. doi: 10.1513/AnnalsATS.201701-006OC. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 4-AP First, Placebo Second | 4-AP 10 mg administered 3 hours before normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching 4-AP administered 3 hours before normal sleep time on second study night. |
| FG001 | Placebo First, 4-AP Second | Placebo-matching 4-AP administered 3 hours before normal sleep time on first study night, then a 1-week non-treatment period, then 4-AP administered 3 hours before normal sleep time on second study night. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Study Night |
| |||||||||||||
| Second Study Night |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Analyzed Participants | All participants who were randomized, completed both study nights, and were included in the analysis. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Posted | Median | Inter-Quartile Range | percentage of wakefulness value | 1 night |
|
2 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo: Placebo 3 hrs before sleep | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment | Headache after 1 hour from administration of dalfampridine, spontaneously recovered after approximately 1.5 hours |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrew Wellman, MD, PhD | Brigham and women's Hospital | awellman@rics.bwh.harvard.edu |
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| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D015761 | 4-Aminopyridine |
| ID | Term |
|---|---|
| D000631 | Aminopyridines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
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| Drug |
Dalfampridine 10 mg extended release 3 hrs before sleep |
|
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Placebo: Placebo 3 hrs before sleep |
| OG001 | Dalfampridine | Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | %max/cmH2O | 1 night |
|
|
|
|
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Dalfampridine | Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep | 0 | 10 | 0 | 10 | 1 | 10 |
|
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| D020919 |
| Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |