Trial Outcomes & Findings for Mechanisms of Sleep Disruption Hyperalgesia (NCT NCT01794689)

Last Updated: 2019-08-02

Results Overview

The area of secondary hyperalgesia (2HA) to mechanical stimulation was quantified by stimulating along eight linear paths near the capsaicin treated site using a 15 gram nonpainful von Frey filament. Stimulation occurred until the participant reported a change in sensation from which a border was marked on the skin. The degree of 2HA was assessed by measuring the total surface area (mm\^2) of the marked borders. Data were collapsed by group to analyze the effects of FA vs US, irrespective of randomization group. Our Primary Secondary Hyperalgesia outcome was measured prior to injection of either morphine or placebo.

Recruitment status

COMPLETED

Study phase

Target enrollment

100 participants

Primary outcome timeframe

Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep

Results posted on

2019-08-02

Participant Flow

During screening for the study we evaluated whether participants were generally healthy, pain free, and good sleepers. We screened 255 to obtain 100 participants who met criteria and were randomized to the experimental portion of the study. The experimental phase occurred at an inpatient clinical research unit.

Participant milestones

Participant milestones
Measure	Morphine US Then Morphine FA Participants randomized to receive Morphine and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.	Morphine FA Then Morphine US Participants randomized to receive Morphine and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.	Placebo US Then Placebo FA Participants randomized to receive the saline placebo and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.	Placebo FA Then Placebo US Participants randomized to receive the saline placebo and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.
Intervention 1 (2 Nights) STARTED	25	29	24	22
Intervention 1 (2 Nights) COMPLETED	20	27	21	18
Intervention 1 (2 Nights) NOT COMPLETED	5	2	3	4
Washout (2 Weeks) STARTED	20	27	21	18
Washout (2 Weeks) COMPLETED	20	27	21	18
Washout (2 Weeks) NOT COMPLETED	0	0	0	0
Intervention 2 (2 Nights) STARTED	20	27	21	18
Intervention 2 (2 Nights) COMPLETED	20	27	21	18
Intervention 2 (2 Nights) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Morphine US Then Morphine FA Participants randomized to receive Morphine and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.	Morphine FA Then Morphine US Participants randomized to receive Morphine and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.	Placebo US Then Placebo FA Participants randomized to receive the saline placebo and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.	Placebo FA Then Placebo US Participants randomized to receive the saline placebo and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.
Intervention 1 (2 Nights) Withdrawal by Subject	3	0	2	4
Intervention 1 (2 Nights) Protocol Violation	1	0	1	0
Intervention 1 (2 Nights) Physician Decision	1	1	0	0
Intervention 1 (2 Nights) Adverse Event	0	1	0	0

Baseline Characteristics

Mechanisms of Sleep Disruption Hyperalgesia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Morphine US Then Morphine FA n=25 Participants Participants randomized to receive Morphine and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.	Morphine FA Then Morphine US n=29 Participants Participants randomized to receive Morphine and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.	Placebo US Then Placebo FA n=24 Participants Participants randomized to receive the saline placebo and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.	Placebo FA Then Placebo US n=22 Participants Participants randomized to receive the saline placebo and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.	Total n=100 Participants Total of all reporting groups
Age, Continuous	27.1348 years STANDARD_DEVIATION 5.97835 • n=5 Participants	29.6819 years STANDARD_DEVIATION 7.54226 • n=7 Participants	27.3609 years STANDARD_DEVIATION 5.22747 • n=5 Participants	27.7272 years STANDARD_DEVIATION 8.18124 • n=4 Participants	28.0581 years STANDARD_DEVIATION 6.81392 • n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	15 Participants n=7 Participants	12 Participants n=5 Participants	17 Participants n=4 Participants	58 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	5 Participants n=4 Participants	42 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants	37 Participants n=21 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	14 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	45 Participants n=21 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Body Mass Index	26.1490 kg/m^2 STANDARD_DEVIATION 4.16713 • n=5 Participants	25.2645 kg/m^2 STANDARD_DEVIATION 3.95007 • n=7 Participants	25.8440 kg/m^2 STANDARD_DEVIATION 3.63156 • n=5 Participants	25.7134 kg/m^2 STANDARD_DEVIATION 4.17552 • n=4 Participants	25.7235 kg/m^2 STANDARD_DEVIATION 3.93648 • n=21 Participants

PRIMARY outcome

Timeframe: Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep

Outcome measures

Outcome measures
Measure	Morphine US n=47 Participants Participants that received morphine with Uninterrupted sleep (US).	Morphine FA n=47 Participants Participants that received morphine with forced awakenings (FA).	Placebo US n=39 Participants Participants that received placebo with Uninterrupted sleep (US).	Placebo FA n=39 Participants Participants that received placebo with forced awakenings (FA).
Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings	1276.25 mm^2 Standard Deviation 1096.761	1582.67 mm^2 Standard Deviation 1590.784	1302.93 mm^2 Standard Deviation 1301.457	1447.9 mm^2 Standard Deviation 1322.52

SECONDARY outcome

Timeframe: Next day after 2 nights of forced awakenings or uninterrupted sleep

Population: Each participant had to do four visits and two testing sessions to be termed complete. The data needed for analysis for this outcome measure was obtained from some participants but not all who completed or couldn't complete the entire study. This explains the differences in the number of units analyzed.

After 2 nights of forced awakenings and after two nights of uninterrupted sleep, opioid analgesia will be assessed by an analgesia index. The analgesia index is calculated using withdrawal latency during cold pressor testing (lasting maximum of 300 seconds). Cold Pressor Testing is done before and after morphine or placebo injection. The difference in withdrawal time before and after morphine or placebo injection is the analgesia index with a minimum score of -300 seconds and maximum score of 300 seconds. These data were log transformed. Mean analgesia index was then calculated for each group. Higher means represent greater analgesia.

Outcome measures

Outcome measures
Measure	Morphine US n=48 cold pressor test Participants that received morphine with Uninterrupted sleep (US).	Morphine FA n=45 cold pressor test Participants that received morphine with forced awakenings (FA).	Placebo US n=42 cold pressor test Participants that received placebo with Uninterrupted sleep (US).	Placebo FA n=39 cold pressor test Participants that received placebo with forced awakenings (FA).
Opioid Analgesia as Assessed by Analgesia Index (Seconds)	0.315 seconds (log transformed) Standard Deviation 0.540	0.156 seconds (log transformed) Standard Deviation 0.712	-0.124 seconds (log transformed) Standard Deviation 0.346	-0.006 seconds (log transformed) Standard Deviation 0.263

SECONDARY outcome

Timeframe: Next day after 2 nights of forced awakenings or uninterrupted sleep, every 60 minutes up to 7 hours

Population: For some participants we could not collect blood samples for all time points and testing sessions. This explains the differences in the numbers of samples analyzed at various timepoints.

After 2 nights of forced awakenings, and two nights of uninterrupted sleep, blood is drawn (approximately every 60 minutes) during quantitative sensory testing; 4 hours pre-morphine/placebo administration and 2 hours post-morphine/placebo administration to examine markers of inflammation. Two blood samples for each participant are analyzed at 7 separate time points. The marker of inflammation assessed is the number of peripheral blood mononuclear cells expressing Interleukin-6 (IL-6), and the outcome measure represents the mean change in IL-6 levels pre and post stimulation with lipopolysaccharide (LPS). Cellular IL-6 expression was was quantified via flow cytometry.

Outcome measures

Outcome measures
Measure	Morphine US n=265 blood samples Participants that received morphine with Uninterrupted sleep (US).	Morphine FA n=256 blood samples Participants that received morphine with forced awakenings (FA).	Placebo US n=225 blood samples Participants that received placebo with Uninterrupted sleep (US).	Placebo FA n=213 blood samples Participants that received placebo with forced awakenings (FA).
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 1	41.98 percentage of IL-6 expression Standard Deviation 21.18	51.82 percentage of IL-6 expression Standard Deviation 21.13	42.91 percentage of IL-6 expression Standard Deviation 19.53	43.32 percentage of IL-6 expression Standard Deviation 19.04
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 2	45.44 percentage of IL-6 expression Standard Deviation 22.95	51.84 percentage of IL-6 expression Standard Deviation 20.34	42.93 percentage of IL-6 expression Standard Deviation 21.81	43.79 percentage of IL-6 expression Standard Deviation 18.01
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 3	45.99 percentage of IL-6 expression Standard Deviation 19.12	48.99 percentage of IL-6 expression Standard Deviation 18.96	40.76 percentage of IL-6 expression Standard Deviation 20.1	41.65 percentage of IL-6 expression Standard Deviation 21.87
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 4	43.96 percentage of IL-6 expression Standard Deviation 18.2	46.94 percentage of IL-6 expression Standard Deviation 17.81	39.06 percentage of IL-6 expression Standard Deviation 20.48	41.34 percentage of IL-6 expression Standard Deviation 21.36
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 5	38.67 percentage of IL-6 expression Standard Deviation 17.93	43.45 percentage of IL-6 expression Standard Deviation 18.3	38.71 percentage of IL-6 expression Standard Deviation 19.11	34.63 percentage of IL-6 expression Standard Deviation 20.74
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 6	36.83 percentage of IL-6 expression Standard Deviation 19.39	39.15 percentage of IL-6 expression Standard Deviation 21.23	35.64 percentage of IL-6 expression Standard Deviation 18.58	36.28 percentage of IL-6 expression Standard Deviation 19.38
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation Timepoint 7	36.47 percentage of IL-6 expression Standard Deviation 18.9	39.92 percentage of IL-6 expression Standard Deviation 19.6	35.49 percentage of IL-6 expression Standard Deviation 17.03	35.25 percentage of IL-6 expression Standard Deviation 19.35

OTHER_PRE_SPECIFIED outcome

Timeframe: Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep.

Population: Each participant had to do four visits to be termed complete. The data needed for analysis for this outcome measure was obtained from some participants but not all who completed or couldn't complete the entire study. This explains the differences in the numbers analyzed for each total sleep time.

The degree of sleep deprivation will be assessed by total sleep time (TST) in minutes during the uninterrupted sleep condition compared to the forced awakenings conditions.

Outcome measures

Outcome measures
Measure	Morphine US n=25 Participants Participants that received morphine with Uninterrupted sleep (US).	Morphine FA n=29 Participants Participants that received morphine with forced awakenings (FA).	Placebo US n=24 Participants Participants that received placebo with Uninterrupted sleep (US).	Placebo FA n=22 Participants Participants that received placebo with forced awakenings (FA).
Total Sleep Time TST: Uninterrupted Sleep-Night 1	442.8909 minutes Standard Deviation 23.06461	425.0280 minutes Standard Deviation 52.40921	443.2375 minutes Standard Deviation 38.99631	435.1467 minutes Standard Deviation 29.12669
Total Sleep Time TST: Uninterrupted Sleep-Night 2	435.2045 minutes Standard Deviation 41.16120	420.1375 minutes Standard Deviation 71.39364	439.0417 minutes Standard Deviation 47.06713	441.1400 minutes Standard Deviation 35.93814
Total Sleep Time TST: Forced Awakenings-Night 1	217.4556 minutes Standard Deviation 46.00094	225.4192 minutes Standard Deviation 38.47452	235.1727 minutes Standard Deviation 50.91526	252.0950 minutes Standard Deviation 32.70550
Total Sleep Time TST: Forced Awakenings-Night 2	270.3333 minutes Standard Deviation 35.23125	258.1083 minutes Standard Deviation 29.47026	267.7714 minutes Standard Deviation 16.90080	261.9941 minutes Standard Deviation 32.01372

Adverse Events

Morphine US

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Morphine FA

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo US

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo FA

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Morphine US n=52 participants at risk Participants that received morphine with Uninterrupted sleep (US).	Morphine FA n=49 participants at risk Participants that received morphine with forced awakenings (FA).	Placebo US n=42 participants at risk Participants that received placebo with Uninterrupted sleep (US).	Placebo FA n=43 participants at risk Participants that received placebo with forced awakenings (FA).
Cardiac disorders Hypotension	3.8% 2/52 • Number of events 2 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Gastrointestinal disorders Nausea	11.5% 6/52 • Number of events 8 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	10.2% 5/49 • Number of events 8 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Gastrointestinal disorders Vomiting	7.7% 4/52 • Number of events 5 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	10.2% 5/49 • Number of events 9 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Nervous system disorders Dizziness	5.8% 3/52 • Number of events 3 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	4.1% 2/49 • Number of events 4 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Nervous system disorders Headache	5.8% 3/52 • Number of events 3 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Gastrointestinal disorders Stomach Pain	0.00% 0/52 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	2.0% 1/49 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/52 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	2.3% 1/43 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Skin and subcutaneous tissue disorders Laceration	1.9% 1/52 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	1.9% 1/52 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Cardiac disorders Tachycardia	0.00% 0/52 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	2.0% 1/49 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Cardiac disorders Syncope	0.00% 0/52 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	2.4% 1/42 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/43 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.
Psychiatric disorders Claustrophobia	0.00% 0/52 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/49 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	0.00% 0/42 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.	2.3% 1/43 • Number of events 1 • Participants were enrolled and actively participating in the study across a time frame of four years and 7.5 months. With no scheduling difficulties each participant remained in the study for 5-6 weeks.

Additional Information

Dr. Michael T. Smith, PhD

Johns Hopkins University

Phone: 410-550-7000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place