Effect of Dalfampridine (4-AP) on Genioglossus Muscle Activity in Healthy Adults (APIGLOSS)

The Effect of Dalfampridine (4-aminopyridine) on Genioglossus Muscle Activity During Wakefulness and Sleep in Healthy Control Subjects

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: Dalfampridine

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).

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Sleep Disorders Research Program Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy control subjects

Exclusion Criteria:

• Cardiovascular disease other than well controlled hypertension
• History of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo 3 hrs before sleep
Active Comparator: Dalfampridine	Drug: Dalfampridine; Dalfampridine 10 mg extended release 3 hrs before sleep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 12, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Actual): August 15, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: BWH-2014P001033C