Primary InsomniaNCT01960452
A High Density EEG Comparison of Sleep Patterns in Insomnia
An observational study of Primary Insomnia, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Insomnia, defined as a subjective report of difficulty initiating sleep, maintaining sleep, and/or non-restorative sleep, leads to significant daytime dysfunction and increased health risks. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Insomnia
- What is being tested?
- Serial awakenings
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Sep 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Participants will be recruited from the community and from patients presenting at the Wisconsin Sleep and UW-Psychiatry clinics for insomnia.
Who may be able to join
- 18-45 years old
- English speaking, reading, and writing
- For control subjects: Insomnia Severity Index (ISI) less than or equal to 6 and does not meet criteria for insomnia
- For insomnia subjects: ISI greater than or equal to 7, meets criteria for insomnia, and reports insomnia symptoms for at least 6 months
Who cannot join
- Imminent danger to self or others
- Clinical diagnosis of dementia
- Active Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I disorder or alcohol or drug dependence or abuse
- Other sleep disorders aside from insomnia
- History of significant head trauma or loss of consciousness over 30 minutes
- Regular use of psychotropic medications in past 4 weeks
Show all 14Show fewer
- Regular tobacco use
- Drinking more than 3 caffeinated beverages per day
- Significant neurological or medical illness
- Pregnant, less than 6 months post-partum, or planning to become pregnant during the study
- Left-handedness
- Body Mass Index (BMI) greater than 40
- Apnea Hypopnea Index (AHI) greater than 10 on Apnea Link
- Mini mental status exam score less than 27
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin, Madison
Madison, Wisconsin, 53719
About this study
Official title: A High Density EEG Comparison of Sleep, Sleep Initiation, and Arousal Patterns in Insomnia Patients and Normal Controls
Insomnia, defined as a subjective report of difficulty initiating sleep, maintaining sleep, and/or non-restorative sleep, leads to significant daytime dysfunction and increased health risks. A commonly held hypothesis is that insomnia is caused by a state of hyperarousal, but the neurobiological mechanisms of hyperarousal in insomnia are poorly understood, in part because of limitations in our ability to image the brain during normal human sleep with sufficient temporal resolution. Furthermore, the efficacy of insomnia treatment is judged by subjective report of the patient and demonstration of changes in sleep latency and/or sleep amount which are generally small in magnitude; there are currently no data to demonstrate that insomnia treatments correct any functional abnormalities in the sleep process that likely contribute to neurobehavioral abnormalities and health risks. The goals of the proposed study are to use high density EEG to define abnormalities in specific aspects of sleep in insomnia patients compared to healthy sleeping control subjects to define biomarkers that will both increase our understanding of the pathophysiology of insomnia as well as provide targets to assess treatments for insomnia.
Read the detailed description
Recent advances in electroencephalographic recording techniques have produced new ways to probe the process and function of sleep. Through the use of high-density EEG (hdEEG, up to 256 channels), it is possible to approach the spatial resolution of other brain imaging modalities while affording the millisecond temporal resolution of EEG and providing a direct measure of the underlying brain activity, unlike the indirect and/or secondary biophysical signals of brain hemodynamics/metabolism obtained with PET or SPECT that are suboptimal for exploring the short-lived spatio-temporal dynamics of many brain processes.
Here we used hdEEG to try to characterize topographic changes in sleep EEG expression in individuals with insomnia compared to normal controls. We further used serial awakenings to determine if individuals with insomnia were more likely to subjectively report being awake when they were sleeping, and study instances where a direct confirmation of sleep was followed by a subjective report of wakefulness to see if they are characterized by changes in EEG oscillations.
- Conditions
- Primary Insomnia
- Being tested
- Serial awakenings
- Keywords
- Insomnia, Primary insomnia, High density EEG, Polysomnography, Healthy sleeping controls
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serial awakeningsBehavioural
The first study night will be a baseline sleep recording. The second night will consist of a series of awakenings (using auditory tones) and subsequent periods of falling back asleep in order to examine the cortical dynamics of hyperarousal or other dysfunction during these two critical sleep processes in insomnia.
| Study group | Role | What they receive |
|---|---|---|
| Primary insomnia | Participants classified as having insomnia through clinical interview, questionnaires, actigraphy, and sleep log data as well as meeting other eligibility criteria. Receives: Behavioral: Serial awakenings | |
| Healthy sleeping controls | Participants classified as having healthy sleepy through clinical interview, questionnaires, actigraphy, and sleep log data as well as meeting other eligibility criteria. Receives: Behavioral: Serial awakenings |
What is being measured
The primary outcome is the main question the study is designed to answer.
EEG Power During Sleep
The difference in spontaneous NREM sleep (stage N2 or N3) EEG power between subjects with insomnia and good sleeping controls measured with 256 channel high-density EEG equipment. Reported here is the median spectral power estimated using Welch's method (MATLAB function pwelch) across all 6 second epochs staged by a registered sleep technician as NREM sleep stage N2 or N3 sleep. The median spectral estimate across all NREM epochs was used to estimate spectral power for each subject as this value is robust to outliers from individual sleep epochs. The Welch's method done in this way estimates frequency content in .33 Hz bins which are then averaged across the spindle frequency band range (12 - 16Hz) from the approximate CP1 electrode (channel 89). The value reported below is the MEAN of the median spectral estimate. Higher values represent more spindle band activity. This frequency range and location showed the most consistent difference between groups across outcome measures.
Measured: Individual night of sleep recorded on average within 4 weeks of enrollment (Night 1, Baseline EEG)
EEG Power Examined Before Arousal From Sleep on Serial Awakening Night
The difference in 30 seconds of spontaneous NREM (stage N2 or N3) sleep EEG power prior to serial awakening between subjects with insomnia and good sleeping controls measured with 256 channel high-density EEG equipment. Reported here is the median spectral power estimated using Welch's method (2 second epochs) of the 30 seconds of NREM sleep stage N2 or N3 sleep immediately prior to the 40dB tone played to initiate a serial awakening sequence. The median spectral estimate across epochs was used to estimate spectral power for each subject as this value is robust to outliers from individual epochs. The Welch's method done in this way estimates frequency content in .5 Hz bins which are then averaged across the spindle frequency band range (12 - 16Hz) from the approximate CP1 electrode (channel 89). Each subject had between 4 - 10 serial awakenings from NREM sleep. The value reported below is the MEAN of the median spectral estimate. Higher values represent more spindle band activity.
Measured: 30 seconds of NREM sleep prior to serial awakening (Night 2, Serial Awakening EEG)
EEG Power Examined as Subjects Fall Asleep on Serial Awakening Night
The difference in 30 seconds of spontaneous falling asleep EEG power between subjects with insomnia and good sleeping controls measured with 256 channel high-density EEG equipment. Reported here is the median spectral power estimated using Welch's method with 2 second epochs from the 30 seconds of sleep immediately following a serial awakening (starting after the last waking epoch) that resulted in the subject reaching 5 minutes of stable sleep averaged across the spindle frequency band range 12 - 16Hz from the approximate CP1 electrode (channel 89) and across all serial awakening falling asleep periods for each subject. Each subject had between 4 - 8 falling asleep periods that resulted in 5 minutes of stable sleep within 30 minutes of the serial awakening attempt. The value reported below is the MEAN of the median spectral estimate. Higher values represent more spindle band activity.
Measured: 30 seconds of falling asleep EEG immediately after the first non-waking epoch following a serial awakening and proceeding 5 minutes of stable sleep (Night 2, Serial Awakening EEG)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary InsomniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Meredith E Rumble, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960452
- Sponsor's protocol ID
- 2013-1613
- Other IDs
- HSC-2013-0019
- Status last verified
- Nov 2024
- First submitted
- 4 Oct 2013
- Last updated
- 9 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A High Density EEG Comparison of Sleep, Sleep Initiation, and Arousal Patterns in Insomnia Patients and Normal Controls
- ClinicalTrials.gov ID
- NCT01960452
- Acronym / sponsor ID
- 2013-1613
- Conditions
- Primary Insomnia
- Keywords
- Insomnia, Primary insomnia, High density EEG, Polysomnography, Healthy sleeping controls
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Oct 2013
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 10 Oct 2013 (estimated)
- Results
- Posted 9 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Insomnia, defined as a subjective report of difficulty initiating sleep, maintaining sleep, and/or non-restorative sleep, leads to significant daytime dysfunction and increased health risks. A commonly held hypothesis is that insomnia is caused by a state of hyperarousal, but the neurobiological mechanisms of hyperarousal in insomnia are poorly understood, in part because of limitations in our ability to image the brain during normal human sleep with sufficient temporal resolution. Furthermore, the efficacy of insomnia treatment is judged by subjective report of the patient and demonstration of changes in sleep latency and/or sleep amount which are generally small in magnitude; there are currently no data to demonstrate that insomnia treatments correct any functional abnormalities in the sleep process that likely contribute to neurobehavioral abnormalities and health risks. The goals of the proposed study are to use high density EEG to define abnormalities in specific aspects of sleep in insomnia patients compared to healthy sleeping control subjects to define biomarkers that will both increase our understanding of the pathophysiology of insomnia as well as provide targets to assess treatments for insomnia.
Detailed description
Recent advances in electroencephalographic recording techniques have produced new ways to probe the process and function of sleep. Through the use of high-density EEG (hdEEG, up to 256 channels), it is possible to approach the spatial resolution of other brain imaging modalities while affording the millisecond temporal resolution of EEG and providing a direct measure of the underlying brain activity, unlike the indirect and/or secondary biophysical signals of brain hemodynamics/metabolism obtained with PET or SPECT that are suboptimal for exploring the short-lived spatio-temporal dynamics of many brain processes.
Here we used hdEEG to try to characterize topographic changes in sleep EEG expression in individuals with insomnia compared to normal controls. We further used serial awakenings to determine if individuals with insomnia were more likely to subjectively report being awake when they were sleeping, and study instances where a direct confirmation of sleep was followed by a subjective report of wakefulness to see if they are characterized by changes in EEG oscillations.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary insomnia | – | Behavioral: Serial awakeningsParticipants classified as having insomnia through clinical interview, questionnaires, actigraphy, and sleep log data as well as meeting other eligibility criteria. |
| Healthy sleeping controls | – | Behavioral: Serial awakeningsParticipants classified as having healthy sleepy through clinical interview, questionnaires, actigraphy, and sleep log data as well as meeting other eligibility criteria. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Participants will be recruited from the community and from patients presenting at the Wisconsin Sleep and UW-Psychiatry clinics for insomnia.
Key inclusion criteria (4 listed)
- 18-45 years old
- English speaking, reading, and writing
- For control subjects: Insomnia Severity Index (ISI) less than or equal to 6 and does not meet criteria for insomnia
- For insomnia subjects: ISI greater than or equal to 7, meets criteria for insomnia, and reports insomnia symptoms for at least 6 months
Key exclusion criteria (14 listed)
- Imminent danger to self or others
- Clinical diagnosis of dementia
- Active Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I disorder or alcohol or drug dependence or abuse
- Other sleep disorders aside from insomnia
- History of significant head trauma or loss of consciousness over 30 minutes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Serial awakeningsThe first study night will be a baseline sleep recording. The second night will consist of a series of awakenings (using auditory tones) and subsequent periods of falling back asleep in order to examine the cortical dynamics of hyperarousal or other dysfunction during these two critical sleep processes in insomnia. | Behavioural | Healthy sleeping controls, Primary insomnia |
Primary outcome
EEG Power During Sleep
Time frame: Individual night of sleep recorded on average within 4 weeks of enrollment (Night 1, Baseline EEG)
The difference in spontaneous NREM sleep (stage N2 or N3) EEG power between subjects with insomnia and good sleeping controls measured with 256 channel high-density EEG equipment. Reported here is the median spectral power estimated using Welch's method (MATLAB function pwelch) across all 6 second epochs staged by a registered sleep technician as NREM sleep stage N2 or N3 sleep. The median spectral estimate across all NREM epochs was used to estimate spectral power for each subject as this value is robust to outliers from individual sleep epochs. The Welch's method done in this way estimates frequency content in .33 Hz bins which are then averaged across the spindle frequency band range (12 - 16Hz) from the approximate CP1 electrode (channel 89). The value reported below is the MEAN of the median spectral estimate. Higher values represent more spindle band activity. This frequency range and location showed the most consistent difference between groups across outcome measures.
EEG Power Examined Before Arousal From Sleep on Serial Awakening Night
Time frame: 30 seconds of NREM sleep prior to serial awakening (Night 2, Serial Awakening EEG)
The difference in 30 seconds of spontaneous NREM (stage N2 or N3) sleep EEG power prior to serial awakening between subjects with insomnia and good sleeping controls measured with 256 channel high-density EEG equipment. Reported here is the median spectral power estimated using Welch's method (2 second epochs) of the 30 seconds of NREM sleep stage N2 or N3 sleep immediately prior to the 40dB tone played to initiate a serial awakening sequence. The median spectral estimate across epochs was used to estimate spectral power for each subject as this value is robust to outliers from individual epochs. The Welch's method done in this way estimates frequency content in .5 Hz bins which are then averaged across the spindle frequency band range (12 - 16Hz) from the approximate CP1 electrode (channel 89). Each subject had between 4 - 10 serial awakenings from NREM sleep. The value reported below is the MEAN of the median spectral estimate. Higher values represent more spindle band activity.
EEG Power Examined as Subjects Fall Asleep on Serial Awakening Night
Time frame: 30 seconds of falling asleep EEG immediately after the first non-waking epoch following a serial awakening and proceeding 5 minutes of stable sleep (Night 2, Serial Awakening EEG)
The difference in 30 seconds of spontaneous falling asleep EEG power between subjects with insomnia and good sleeping controls measured with 256 channel high-density EEG equipment. Reported here is the median spectral power estimated using Welch's method with 2 second epochs from the 30 seconds of sleep immediately following a serial awakening (starting after the last waking epoch) that resulted in the subject reaching 5 minutes of stable sleep averaged across the spindle frequency band range 12 - 16Hz from the approximate CP1 electrode (channel 89) and across all serial awakening falling asleep periods for each subject. Each subject had between 4 - 8 falling asleep periods that resulted in 5 minutes of stable sleep within 30 minutes of the serial awakening attempt. The value reported below is the MEAN of the median spectral estimate. Higher values represent more spindle band activity.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meredith E Rumble, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Insomnia, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EEG Power During Sleep (time frame: Individual night of sleep recorded on average within 4 weeks of enrollment (Night 1, Baseline EEG)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2025.