Hyper-Arousal in Chronic Primary Insomnia

Multi-Level Assessment of Physiologic Hyper-Arousal in Chronic Primary Insomnia: A Case Control Study

The purpose of this study is to determine whether individuals with chronic insomnia disorder have a higher degree of physiologic arousal (resulting in their trouble sleeping) than good sleepers. The primary goal is to perform a rigorous quantitative assessment of physiologic hyper-arousal across two domains (autonomic nervous system and neurophysiology) in patients with chronic primary insomnia as compared to good sleepers matched for sex, age, body mass index (BMI) and race/ethnicity.

Study Overview

• Status: Completed
• Conditions: Chronic Insomnia

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Insomniacs and good sleepers

Description

Inclusion Criteria for Insomniacs:

• Men and women with primary insomnia of at least 3 months in duration
• ages 21-65 years old
• BMI <35 kg/m2 to enable microneurography
• Moderate to severe insomnia based on the Insomnia Severity Index (ISI) questionnaire
• Pittsburgh Sleep Quality Index (PSQI) > 5
• Self-reported habitual sleep duration < 6.5 hours

Inclusion criteria for good sleepers:

• 21-65 years old men and women with BMI <35 kg/m2
• No insomnia based on ISI questionnaire
• Self-reported habitual sleep duration ≥ 6.5 hours but < 9 hours
• PSQI<5
• Sleep efficiency on PSG with TRT of 8 hours > 85%
• No history of mental illness, shift work, circadian rhythm disorders

Exclusion criteria for both insomniacs and good sleepers:

• Sleep disorders other than insomnia as assessed by screening PSG (apnea-hypopnea index or AHI ≥ 10, PLM arousal index ≥ 5)
• Circadian rhythm sleep disorders
• Diabetic based on HbA1c ≥ 6.5 %. For those with HbA1c ≥ 6.0 but <6.5%, the non-diabetic condition will be confirmed by 2-h oral glucose tolerance test
• History of meeting DSM-IVR criteria based on the Mini International Neuropsychiatric Interview version 6.0 for any major psychiatric disorder
• Unstable or serious medical conditions
• Current, or use within the past month, of psychoactive (other than stable treatment with antidepressants), hypnotic, stimulant or analgesic medications (except occasional non-narcotic analgesics), beta blockers or alpha blockers
• Shift work or other types of self imposed irregular sleep schedules
• Habitual smoking
• Habitual alcohol consumption
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Insomnia group; Assessment of physiologic hyper-arousal across the two following domains: 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.; 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: 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.; Neurophysiologic arousal: recording of multiple sleep latency test (MSLT), recording of wake electroencephalography (EEG), and quantitative sleep EEG recording and analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sympathetic Baroreflex Sensitivity (BRS) Unit	Direct recording of sympathetic nervous activity in a nerve of the lower leg using a micro-electrode.	2 months after enrollment
Systolic Arterial Pressure Reactivity	Increase in blood pressure to stress	within 2 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Sleep Latency Test (MSLT)	MSLT will be used to objectively quantify tendency to fall asleep (sleep latency).	2 months of enrollment
Heart Rate Variability During Wake and During Sleep	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.	2 months after enrollment
Electroencephalography (EEG) During Wake and Sleep	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.	2 months of enrollment
Noninvasive Beat-to-beat Blood Pressure Monitoring		2 months after enrollment

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Eve Van Cauter, PhD, University of Chicago; Principal Investigator: Babak Mokhlesi, MD, University of Chicago; Principal Investigator: Jason R Carter, PhD, Michigan Technological University

Publications and helpful links

General Publications

• Carter JR, Grimaldi D, Fonkoue IT, Medalie L, Mokhlesi B, Cauter EV. Assessment of sympathetic neural activity in chronic insomnia: evidence for elevated cardiovascular risk. Sleep. 2018 Jun 1;41(6):zsy048. doi: 10.1093/sleep/zsy048. Erratum In: Sleep. 2018 Sep 1;41(9):

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 9, 2016
• Study Completion (Actual): December 20, 2016

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 27, 2014
• First Posted (Estimate): January 29, 2014

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 3, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Insomnia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: 13-1214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO