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Trial record 3 of 39 for:    FLUMAZENIL

Flumazenil for the Treatment of Primary Hypersomnia

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ClinicalTrials.gov Identifier: NCT01183312
Recruitment Status : Completed
First Posted : August 17, 2010
Results First Posted : March 27, 2013
Last Update Posted : December 12, 2017
Sponsor:
Collaborator:
Georgia Research Alliance
Information provided by (Responsible Party):
Lynn Marie Trotti, Emory University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hypersomnia
Primary Hypersomnia
Idiopathic Hypersomnia
Narcolepsy Without Cataplexy
Intervention Drug: Flumazenil
Enrollment 10
Recruitment Details Participants were recruited from the Sleep Center of the Emory Clinic, in Atlanta, Georgia, USA, between December 2010 and October 2011.
Pre-assignment Details 12 patients were enrolled; of these, 2 were excluded prior to randomization because screening laboratory test results were abnormal.
Arm/Group Title Placebo First, Then Flumazenil Flumazenil First, Then Placebo
Hide Arm/Group Description Placebo administered sublingually three times during the first study day, followed by a washout of at least 7 days, then flumazenil administered sublingually three times during the second study day. Flumazenil administered sublingually three times during the first study day (as 12 mg, then 6 mg, then 6 mg, at approximately 3 hour intervals), followed by a washout of at least 7 days, then placebo administered sublingually three times on the second study day.
Period Title: First Intervention Day
Started 5 5
Completed 5 5
Not Completed 0 0
Period Title: Washout Period of at Least 1 Week
Started 5 5
Completed 5 5
Not Completed 0 0
Period Title: Second Intervention Day
Started 5 5
Completed 5 5
Not Completed 0 0
Arm/Group Title Placebo First, Then Flumazenil Flumazenil First, Then Placebo Total
Hide Arm/Group Description Placebo during the first intervention day and sublingual flumazenil during the second intervention day (after washout period). Sublingual flumazenil during the first intervention day and placebo during the second intervention day (after washout period). Total of all reporting groups
Overall Number of Baseline Participants 5 5 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 10 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
 100.0%
5
 100.0%
10
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 5 participants 10 participants
33.6  (13.3) 41.8  (18.1) 37.7  (15.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 10 participants
Female
5
 100.0%
5
 100.0%
10
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants 5 participants 10 participants
5 5 10
1.Primary Outcome
Title Change in Psychomotor Vigilance Task (PVT) Median Reaction Time
Hide Description The PVT measures the reaction time to button press following the presentation of a visual stimulus, reported here as the median reaction time for multiple presentations during the 10 minute task. The measure used was the change in median reaction time from baseline to drug administration, where the median reaction time at each of the time points (below) was averaged to provide a single on-treatment value for median reaction time. The measure was then calculated as baseline value - treatment value, such that higher numbers denote improvement from baseline.
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: msec
-9.86  (28.2) -4.46  (63.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method wilcoxon signed rank (paired)
Comments [Not Specified]
2.Secondary Outcome
Title PVT Additional Measure #1, Change in Lapse Frequency
Hide Description A PVT lapse is defined as a reaction time exceeding 500 msec following the presentation of a single stimulus, which are then summed for the entire 10 minute PVT testing period. The measure used was the change in the frequency of lapses from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: number of lapses during PVT testing
-3.3  (6.9) -2.6  (8.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Wilcoxon Signed Rank (paired)
Comments [Not Specified]
3.Secondary Outcome
Title PVT Additional Measure #2, Change in Duration of Lapse Domain
Hide Description The PVT duration of lapse domain is defined as the reciprocal of the reaction time averaged across the slowest 10% of responses. The measure used was the change in duration of lapse domain from baseline to drug administration (calculated as baseline value - average value with study drug, where lower numbers denote improvement from baseline).
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: 1/msec
0.18  (0.30) 0.25  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method Wilcoxon Signed Rank (paired)
Comments [Not Specified]
4.Secondary Outcome
Title PVT Additional Measure #3, Change in Optimum Response Times
Hide Description The optimum response times is defined as the reciprocal of the reaction time averaged across the fastest 10% of responses. The measure used was the change in optimum response time from baseline to following drug administration (calculated as baseline value - average value with study drug, where lower numbers denote improvement from baseline).
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: 1/msec
-0.02  (0.27) -0.04  (0.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments [Not Specified]
Method Wilcoxon Signed Rank (paired)
Comments [Not Specified]
5.Secondary Outcome
Title PVT Additional Measure #4, Change in False Response Frequency
Hide Description The false response frequency is defined as the number of button presses when no stimulus is presented. The measure used was the change in false response frequency from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: number of false starts
0.09  (0.56) -0.38  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Wilcoxon Signed Rank (paired)
Comments [Not Specified]
6.Secondary Outcome
Title PVT Additional Measure #5, Change in Visual Analog Scale Rating of Sleepiness at the Completion of PVT
Hide Description At the end of the 10 minute PVT testing period, subjects were asked to rate their current level of sleepiness along a line, which was transformed into a numeric value from 1-10, such that high levels indicated more severe subjective sleepiness. The measure used was the change in this rating from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.23  (1.49) 1.01  (2.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method Wilcoxon Signed Rank (paired)
Comments [Not Specified]
7.Secondary Outcome
Title Change in Stanford Sleepiness Scale
Hide Description The Stanford Sleepiness Scale (SSS) is a subjective rating of sleepiness, with score ranging from 1 to 7, where higher values reflect more severe sleepiness. The measure used was change in SSS from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time Frame 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (all randomized subjects were included)
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.84  (1.68) 0.26  (1.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sublingual Flumazenil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Wilcoxon Signed Rank (paired)
Comments [Not Specified]
8.Secondary Outcome
Title Electroencephalogram (EEG) Power
Hide Description EEG signals reflect the state of excitability of the cerebral cortex and correlate highly with levels of behavioral arousal. This is quantifiable as ‘power’ of the signal (microvolts squared/signal frequency). The EEG signals will be acquired and stored for off-line power analysis and comparison between treatment conditions.
Time Frame following drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
EEG signal processing analyses have not been performed. This would require an additional set of extensive analyses, very distinct from the statistics performed for the other study outcomes. EEG data were collected for possible future analyses, pending resources and expertise, and as such we have no data to report here.
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description:
Sublingual placebo administered three times over a single day, in either first or second intervention period
Sublingual flumazenil administered three times over a single day (12 mg, 6 mg, 6 mg dosing), in either the first or second intervention period
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Symptoms experienced within 24 hours of drug administration
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Sublingual Flumazenil
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Placebo Sublingual Flumazenil
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Sublingual Flumazenil
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Sublingual Flumazenil
Affected / at Risk (%) Affected / at Risk (%)
Total   4/10 (40.00%)   9/10 (90.00%) 
Musculoskeletal and connective tissue disorders     
back pain  0/10 (0.00%)  1/10 (10.00%) 
Nervous system disorders     
feeling "dizzy", "lightheaded", or "spacey"  4/10 (40.00%)  3/10 (30.00%) 
headache (during or following drug administration)  0/10 (0.00%)  4/10 (40.00%) 
feeling "jittery"  0/10 (0.00%)  1/10 (10.00%) 
Psychiatric disorders     
feeling of "panic", "anxiety", or "uneasy"  1/10 (10.00%)  1/10 (10.00%) 
feeling "giggly" or "high"  0/10 (0.00%)  1/10 (10.00%) 
feeling dysphoria or "drugged"  0/10 (0.00%)  1/10 (10.00%) 
EEG power was specified as a secondary outcome measure. Second-by-second manual artifact removal has been necessary to ensure interpretable data. This artifact removal is in progress and results will be reported separately.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Lynn Marie Trotti
Organization: Emory University School of Medicine
Phone: 404-728-4752
EMail: lbecke2@emory.edu
Layout table for additonal information
Responsible Party: Lynn Marie Trotti, Emory University
ClinicalTrials.gov Identifier: NCT01183312     History of Changes
Other Study ID Numbers: IRB00044836
First Submitted: August 9, 2010
First Posted: August 17, 2010
Results First Submitted: January 11, 2013
Results First Posted: March 27, 2013
Last Update Posted: December 12, 2017