Manipulating and Optimising Brain Rhythms for Enhancement of Sleep

NCT05011773 | Completed DMC

• 1 other identifier: 20/PR/0409
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of sleep disturbances is mainly attempted through drug administration. However, certain drugs are associated with unwanted side effects or residual effects upon awakening (e.g. sleepiness, ataxia) which can increase the risks of falls and fractures. In addition, there can be systemic consequences of long-term use. An alternative method of manipulating sleep is by stimulating the brain to influence the electroencephalogram (EEG). To date, there have been mixed results from stimulating superficial areas of the brain and, as far as we know, there has been no systematic attempt to influence deep brain activity. Many patients suffering from movement disorders, such as Parkinson's Disease (PD) and Multiple Systems Atrophy (MSA), also have disrupted sleep. Currently, at stages where drug treatment no longer offers adequate control of their motor symptoms, these patients are implanted with a deep brain stimulation system. This involves depth electrodes which deliver constant pulse stimulation to the targeted area. A similar system is used in patients with severe epilepsy, as well as some patients with chronic pain. The aim of this feasibility study is to investigate whether we can improve sleep quality in patients with deep brain stimulators by delivering targeted stimulation patterns during specific stages of sleep. We will only use stimulation frequencies that have been proven to be safe for patients and frequently used for clinical treatment of their disorder. We will examine the structure and quality of sleep as well as how alert patients are when they wake up, while also monitoring physiological markers such as heart rate and blood pressure. Upon awakening, we will ask the patients to provide their subjective opinion of their sleep and complete some simple tests to see how alert they are compared to baseline condition which would be either stimulation at the standard clinical setting or no stimulation. We hope that our study will open new ways of optimising sleep without the use of drugs, in patients who are implanted with depth electrodes. We also believe that our findings will broaden the understanding of how the activity of deep brain areas influences sleep and alertness.

Conditions

Parkinson Disease; MSA - Multiple System Atrophy; Chronic Pain; Epilepsy

Keywords

sleep; Electroencephalography; Deep brain stimulation

Outcome Measures

Primary Outcomes (2)

• Sleep stages

  Sleep staging will assessed using gold standard sleep polysomnography (Video EEG, EOG, ECG). Sleep stage classification will be assessed by an expert sleep neurophysiologist using standard AASM and other criteria. DBS ON and night and DBS OFF night will be compared to look for the differences in sleep architecture such as total sleep time and duration in sleep phase (N1-3, REM, non-REM and wakefulness)

  4 nights total (2 visits of 2 nights with DBS ON and OFF during each visit). Each night is defined as the period between 2300hrs and 0700 hrs in a windowless, temperature controlled sleep laboratory

• Sleep inertia

  Differences in sleep inertia after DBS ON vs DBS OFF night will be compared using the sleep inertia scale (questionnaire)

  4 nights total (2 visits of 2 nights - same period as outcome 1)

Secondary Outcomes (1)

• Control of sleep

  4 nights total (2 visits of 2 nights - same period as outcome 1)

Other Outcomes (3)

• Heart rate variability

  4 nights total (2 visits of 2 nights - same period as outcome 1)

• Blood pressure

  4 nights total (2 visits of 2 nights - same period as outcome 1)

• Salivary cortisol levels

  4 nights total (2 visits of 2 nights - same period as outcome 1)

Study Arms (1)

Deep brain stimulation

EXPERIMENTAL

All patients have already undergone deep brain stimulation. Results compared "on" and "off" stimulation.

Device: Deep brain stimulation

Interventions

Deep brain stimulation DEVICE

Electrical pulses from implanted generator that has already been implanted for therapeutic reasons

Deep brain stimulation

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Either already implanted with DBS electrodes or undergoing DBS implantation in one of the defined nuclei of interest (for Surrey or Rochester: STN, PPN, Hypothalamus, PAG/PVG - for the Mayo clinic, may use hippocampus or ANT) for standard clinical care during the period of the study
• Male or female, aged 18 to 85
• Be willing and able to give written and oral informed consent
• Ability to complete all required study procedures including travelling to the Sleep Centre and staying overnight
• By the time of the first visit to Surrey, participants should have already had their stimulation settings programmed by the Functional Neurosurgery team and have been stable on the settings for at least two weeks, as per their routine clinical care.
• For patients with chronic pain, they should be stable on their current medication and settings

You may not qualify if:

• Cognitive impairment (judged by the clinician taking consent as not having sufficient mental capacity to understand the study and its requirements). This is including anyone who, in the opinion of the clinician taking consent is unlikely to retain sufficient mental capacity for the duration of their involvement in the study.
• Patients with any other medical condition that would interfere with study conduct or make it unsafe for them to participate. Such conditions may be poorly controlled diabetes, poorly controlled/end stage heart disease, renal failure as well as recurrent, uncontrolled seizures or epilepsy.
• Participants who have started new medication or changed doses 3 weeks prior to a study visit may not be eligible as deemed by the PI of the study.
• Patients on medication that can affect the study results (such as hypnotics - benzodiazepines and analogues), at the discretion of the PI.
• Patients currently taking ketamine
• Alcohol intake exceeding 28 units per week.

Sponsors & Collaborators

• University of Oxford: lead
• Surrey Sleep Research Centre, Surrey, UK: collaborator
• Mayo Clinic: collaborator
• University of California, San Francisco: collaborator

Study Sites (1)

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease; Shy-Drager Syndrome; Chronic Pain; Epilepsy

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Multiple System Atrophy; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Alexander L Green, FRCS(SN)

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Evaluation of symptomatology "on" and "off" deep brain stimulation

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: August 18, 2021
• Study Start: August 3, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: November 4, 2022

Record last verified: 2022-10

Locations

GB (1)