Trial Outcomes & Findings for Hyper-Arousal in Chronic Primary Insomnia (NCT NCT02048878)

Results Overview

Direct recording of sympathetic nervous activity in a nerve of the lower leg using a micro-electrode.

Recruitment status

COMPLETED

Target enrollment

28 participants

Primary outcome timeframe

2 months after enrollment

Results posted on

2020-01-18

Participant Flow

Participant milestones

Participant milestones
Measure	Insomnia Group Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Matched Control Group Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.
Overall Study STARTED	13	15
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hyper-Arousal in Chronic Primary Insomnia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insomnia Group n=13 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Matched Control Group n=15 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Total n=28 Participants Total of all reporting groups
Age, Continuous	40 years STANDARD_DEVIATION 15 • n=93 Participants	35 years STANDARD_DEVIATION 13 • n=4 Participants	37.3 years STANDARD_DEVIATION 14 • n=27 Participants
Sex: Female, Male Female	12 Participants n=93 Participants	10 Participants n=4 Participants	22 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	12 Participants n=93 Participants	13 Participants n=4 Participants	25 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: 2 months after enrollment

Direct recording of sympathetic nervous activity in a nerve of the lower leg using a micro-electrode.

Outcome measures

Outcome measures
Measure	Insomnia Group n=12 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Matched Control Group n=12 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.
Sympathetic Baroreflex Sensitivity (BRS) Unit	-2.1 bursts per 100 heart beats per mm Hg Standard Deviation 1.0	-4.3 bursts per 100 heart beats per mm Hg Standard Deviation 1.3

PRIMARY outcome

Timeframe: within 2 months after enrollment

Increase in blood pressure to stress

Outcome measures

Outcome measures
Measure	Insomnia Group n=12 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Matched Control Group n=12 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.
Systolic Arterial Pressure Reactivity	21 mmHg Standard Deviation 11	14 mmHg Standard Deviation 8

SECONDARY outcome

Timeframe: 2 months of enrollment

Population: One insomnia subject and one good sleeper control could not remain in the laboratory for the entire duration of the test due to personal scheduling issues.

MSLT will be used to objectively quantify tendency to fall asleep (sleep latency).

Outcome measures

Outcome measures
Measure	Insomnia Group n=11 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Matched Control Group n=11 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.
Multiple Sleep Latency Test (MSLT) Nap 1	8.7 minutes Standard Deviation 6.8	11.2 minutes Standard Deviation 8.2
Multiple Sleep Latency Test (MSLT) Nap 2	7.3 minutes Standard Deviation 7.2	9.4 minutes Standard Deviation 6.1
Multiple Sleep Latency Test (MSLT) Nap 3	6.8 minutes Standard Deviation 6.9	5.3 minutes Standard Deviation 3.2
Multiple Sleep Latency Test (MSLT) Nap 4	6.7 minutes Standard Deviation 5.7	6.5 minutes Standard Deviation 6.4
Multiple Sleep Latency Test (MSLT) Nap 5	12.7 minutes Standard Deviation 7.1	8.4 minutes Standard Deviation 7.1

SECONDARY outcome

Timeframe: 2 months after enrollment

Population: The biological signals were recorded but not submitted to the labor-intensive spectral analysis due to end of funding. Summary data were not generated. Therefore, no results on this outcome can be reported.

The balance between sympathetic and parasympathetic nervous control of the heart will be determined by spectral analysis of heart rate variability using continuous electrocardiogram (ECG) recording for 24 hours, including the normal sleep period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 months of enrollment

Population: The biological signals were recorded but not submitted to the labor-intensive spectral analysis due to end of funding. Summary data were not generated. Therefore, no results on this outcome can be reported.

The EEG will be measured continuously during sleep and at frequent intervals during wake. The signal will be submitted to power spectral analysis to examine spectral power in frequency bands that are typical of arousal and in frequency bands that are typical of deep sleep.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 months after enrollment

Population: Two insomnia subjects and 3 control subjects dropped out of the study after completing their first inpatient visit due to scheduling conflicts related to their professional occupation.

Outcome measures

Outcome measures
Measure	Insomnia Group n=10 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.	Matched Control Group n=9 Participants Assessment of physiologic hyper-arousal across the two following domains: 1. Sympathetic neural activity: recording at the level of the muscle by microneurography and at the level of the heart by spectral analysis of heart rate variability from the ECG signal obtained during sleep and wakefulness. 2. Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.
Noninvasive Beat-to-beat Blood Pressure Monitoring Systolic Blood Pressure dipping	7.3 mm Hg Standard Deviation 11.9	15.2 mm Hg Standard Deviation 7.3
Noninvasive Beat-to-beat Blood Pressure Monitoring Diastolic Blood Pressure dipping	3.0 mm Hg Standard Deviation 5.9	6.4 mm Hg Standard Deviation 2.5

Adverse Events

Insomnia Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Matched Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Eve Van Cauter, PhD

University of Chicago

Phone: 773-702-0169

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place