Subcortical Oscillations in Human Sleep Dysregulation

Understanding the Role of Subcortical Oscillations in Human Sleep Dysregulation.

Sleep problems are common in the United States (US) adult population (>50 million), and have a negative impact on quality of life, productivity, and healthcare. A major obstacle to understanding how the brain is involved in human sleep disorders has been the lack of recordings of human brain function, from inside the brain, during the known sleep states.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease; REM Behavior Disorder
• Intervention / Treatment: Other: Sleep, PD and DBS

Detailed Description

Sleep is necessary for life; critically important to the regulation of body and brain function. Sleep problems are common in the U.S. adult population (>50 million), and have a negative impact on quality of life, productivity, and healthcare. A major obstacle to understanding how the brain is involved in human sleep disorders has been the lack of recordings of brain function, from inside the brain, during the known sleep states; non-rapid eye movement (NREM) and rapid eye movement (REM). It is very common for patients with Parkinson's disease (PD) to also have sleep disorders, such as insomnia, restless-leg-syndrome and REM-behavior disorder. One treatment for PD patients is deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS). Despite evidence showing that STN-DBS improves several aspects of sleep behavior in PD subjects, few studies have examined the relationship between brain activity and sleep regulation in human subjects. In this proposal, the investigators will examine sleep in humans by recording brain activity from STN of PD patients who have undergone DBS surgery. The investigators will also test the hypothesis that STN contributes to both the regulation and disruption of normal sleep behavior.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Parkinsons Disease and a documented sleep disorder planning on undergoing bilateral Deep Brain Stimulation surgery at the University of Colorado Hospital.

Description

Inclusion Criteria:

Subjects with Parkinson's Disease (PD) who are planning to have staged, bilateral deep brain stimulation surgery at the University of Colorado Hospital and willing and able to do the following:

1. Have a computer and be willing to use it as part of this study.
2. Be able to learn to use and maintain a wristband-style sleep monitor.
3. Turn off their Implantable Pulse Generator (IPG, implanted battery).
4. Wear a wristband-style sleep monitor for 3 weeks, 6 weeks prior to surgery.
5. Spend one overnight research stay in the UCH Sleep lab, 3 weeks prior to DBS surgery .
6. Spend one overnight research stay in the UCH Sleep lab, immediately prior to IPG surgery, to record brain activity from the DBS electrode .
7. Have a 15 minute surgery to externalize the DBS lead cable to allow overnight recordings to occur.
8. Be pseudo-randomized to one of 2 conditions: OFF stimulation or ON stimulation.
9. Wear a wristband-style sleep monitor for 3 weeks, 3 months post-DBS surgery, in one of the 2 pseudo-randomized conditions.
10. Spend one overnight research stay in the UCH Sleep lab, 4 months post DBS surgery, in one of the pseudo-randomized conditions.

Subjects will have a sleep disorder documented in their medical history as determined by a single question screen for REM sleep behavior disorder.

Exclusion Criteria:

1. Subjects with Parkinson's Disease (PD) who are not planning to have staged, bilateral deep brain stimulation surgery at the University of Colorado Hospital.
2. Subjects without a documented sleep disorder.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group #1; Patients with Parkinsons Disease who will undergo Deep Brain Stimulation surgery. At home sleep monitoring prior to DBS surgery and in patient polysomnography with neural recording after DBS surgery.	Other: Sleep, PD and DBS; Sleep, PD and DBS
Group #2; Patients with Parkinsons Disease who will undergo Deep Brain Stimulation surgery. At home sleep monitoring after DBS surgery with DBS stimulation on at night, and in patient polysomnography after DBS surgery.	Other: Sleep, PD and DBS; Sleep, PD and DBS
Group #3; Patients with Parkinsons Disease who will undergo Deep Brain Stimulation surgery. At home sleep monitoring after DBS surgery with DBS stimulation off at night, and in patient polysomnography after DBS surgery.	Other: Sleep, PD and DBS; Sleep, PD and DBS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring brain physiological activity via local field potentials and correlation to sleep states (REM, non-REM, etc.)	STN LFP activity will be measured by externalized DBS electrodes during in patient polysomnography.	One entire sleep cycle (each cycle is 8-10 hours).
Chronic actigraphy to characterize sleep-wake behavior	The investigators will collect typical sleep-wake behavior-including indirect features of sleep disturbance-by equipping patients with a sleep-monitoring device (ActiGraph AW2) that will record sleep parameters.	3 weeks
Test the functional impact of STN-DBS on sleep-wake behavior through actigraphy	The investigators will examine the impact of STN modulation, via DBS in both On- and Off-Stimulation conditions in separate groups of subjects, on typical sleep-wake behavior.	3 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: John A Thompson, Ph.D., Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Actual): August 2, 2020
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 29, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Polysomnography; Deep Brain Stimulation; Actigraphy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parasomnias; REM Sleep Parasomnias; Parkinson Disease; Mental Disorders; REM Sleep Behavior Disorder
• Other Study ID Numbers: 17-0868

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No