None listed
Conditions
Brief summary
Deep brain stimulation (DBS) is a treatment for Parkinson's disease that uses a small implanted device to send electrical signals to specific areas of the brain, helping to control movement symptoms. While DBS is known to improve movement, less is known about how it affects sleep quality and breathing (pulmonary function) in people with Parkinson's disease. This pilot study aims to find out what types of sleep and breathing problems occur in people with Parkinson's disease who have a DBS device. There are three common brain locations where the DBS device can be placed, and this study will compare how each of these affects sleep and breathing. Participants who already have a DBS device will attend the hospital for an overnight sleep study, and separately for breathing tests, both with their DBS switched on and again with it switched off, so researchers can see the difference stimulation makes. A comparison group of people with Parkinson's disease who don't have DBS (managed with medication only) will also complete the breathing tests, to help researchers understand whether any breathing changes are related to the DBS device itself, to Parkinson's disease more broadly, or to something else. By better understanding how DBS affects sleep and breathing, this research aims to help doctors make more informed decisions about DBS placement and management, and ultimately improve quality of life for people living with Parkinson's disease.
Interventions
This is a Deep Brain Stimulation (DBS) interventional study comparing three DBS groups (Subthalamic nucleus (STN), Caudal Zone incerta (CZi), Globus pallidus interna (GPi), each with 10 subjects, during ON and OFF stimulation (n=30). A medically managed Parkinson’s disease (PD) group (n=40) and a further 20 control subjects will be included. The 3 DBS groups will have sleep and pulmonary interventions during their ON and OFF phase. Each patient will act as their own control when they are evaluat
This is a Deep Brain Stimulation (DBS) interventional study comparing three DBS groups (Subthalamic nucleus (STN), Caudal Zone incerta (CZi), Globus pallidus interna (GPi), each with 10 subjects, during ON and OFF stimulation (n=30). A medically managed Parkinson’s disease (PD) group (n=40) and a further 20 control subjects will be included. The 3 DBS groups will have sleep and pulmonary interventions during their ON and OFF phase. Each patient will act as their own control when they are evaluated OFF DBS. The medically managed breathless patients will be evaluated with the pulmonary interventions only. There is no surgical intervention as part of this clinical trial. Patients with existing DBS devices, in situ for at least 1 year in duration, who fulfil the inclusion and exclusion criteria and consent to participation will undergo sleep and pulmonary interventions. The parameters of the DBS settings are not standardised in the patients. These are based on individual responses to therapy and will be predetermined and stable by the treating neurologist before they take part in this study. The sleep intervention is an overnight polysomnography testing which requires attachment of electrodes to head and body to monitor sleep cycle state (rapid eye movement sleep, stages of sleep, periodic limb movements of sleep), and vital parameters (heart rate, rhythm and oxygen saturation concentration), while the patient sleeps in the controlled environment of the sleep laboratory. This intervention will be performed by a qualified sleep scientist, with the Principal Investigator (PI), a neurologist, present.. The patient would arrive at 8pm for initiation of this study. The sleep study itself will run from 10pm to 6am (the following morning). Once the overnight sleep study is complete, the equipment will be removed from the patient. The patient will then undertake one computer based assessment where their wakefulness will be measured by evaluating the reaction time to a computer generated stimulus. This test will take a further 10 minutes to complete. The sleep intervention will be performed by the patient with the DBS ON with their routine settings running, where no adjustments will be made to the stimulation parameters. The individual settings of patients will vary from patient to patient and is determined by their treating neurologist. Where possible, the overnight polysomnography will also be undertaken in the same patient on a separate visit within 6 months duration from the first, with the DBS turned OFF. The patient will arrive for the sleep study at 8pm and have their DBS device switched OFF by the PI. The sleep study will commence at 10pm and run until 6am the following morning. The wakefulness testing will be completed. And the patient's DBS will be turned back ON by 8am prior to them leaving the laboratory. Similarly the pulmonary testing will be done in PD patients with existing DBS in situ. The patient will attend the laboratory at their designated time for their individual tests. These tests include a lung function testing which is where the patient will be asked to breathing into a tube which measures their lung capacity/parameters including forced vital capacity, total lung volume etc. This will take 40 minutes to complete. This will be followed by a cardiopulmonary testing which entails the patient having electrodes placed to measure their heart rate, and wearing a mask device to measure oxygen concentration. They will be asked to exercise on a bike in an incremental pattern over 15 minutes to determine the response of their cardiopulmonary system to incremental exercise. These are standardised tests performed by trained respiratory scientists in a controlled, safe environment. The PI will be present to ensure comfort and safety for all study participants. When testing the patients in the DBS OFF state, the patient will be asked to attend the laboratory two hours before their test so the PI can switch OFF the DBS device. The DBS will be turned back on by PI once the tests are completed. The DBS patients will also be asked to attend the laboratory on a separate occasion, within 6 months from the first tests, to undertake the Control of Ventilation (COV) study. This test involves the subject being seated and application of saturation probe for monitoring as well as a breathing apparatus with a tight seal round the mouth which measures carbon dioxide and oxygen concentrations. The patient is asked to breathe normally while the investigators adjust the concentration of oxygen and carbon dioxide the patient inhales while measuring their saturation and breathing index. This information is recorded on a digital graph format to interpret. The test takes 30 - 40 minutes to complete with the subject being attached to the apparatus for approximately 15 minutes in total. The remainder of the time is spent setting up the test and apparatus by the scientists. For the medical managed PD patients, the pulmonary tests will only be performed in the ON state which will be defined as 2 hours post last levodopa ingestion. The will undergo the pulmonary testing as described above on two separate occasions too. For all the assessments in the DBS patients, we will switch off the DBS 2 hours before the test is due to start. ON will be defined as two hours post medication duration in the medically managed PD patients. The ON and OFF states will be recorded by using Unified Parkinson's Disease Rating Scale (UPDRS) Motor Part 3. For those patients with DBS in situ, the ON is defined as the DBS functioning normally in the ON state. OFF state in the DBS patients will be considered when the DBS device is turned off by the PI. The parameters of DBS will not be identical for each individual patient. These will vary depending on the therapeutic response for each individual patient, which is considered gold standard practice as no two patients will ever have the same DBS settings due to the variation in clinical symptoms and response to treatment. We will attempt to make reference to this in the analysis and discussion section as a potential confounder . Please note that addressing the relationship of DBS parameters with outcome measures is not the primary aim of this study. Instead, we are attempting to see if there is any correlation with site of DBS insertion (i.e Subthalamic nucleus, Caudal Zona incerta and Globus pallidis interna) and outcome measures. The washout period will be a minimum of 1 month between treatments. Approximate range for DBS parameters are: Amplitude 1.5 - 6.0 milliamps Pulse width 20 - 60 microseconds Frequency 130 - 160 hertz
Sponsors
Dr Srimathy Vijayan: Perron Institute for Neurological and Translational Science
Study design
Allocation
Non-randomised trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
For DBS PD patients: • Clinical diagnosis of Parkinson’s disease made by a Movement disorder specialist using the Movement Disorder Society criteria • DBS insertion of at least 1 year duration • Male or female sex aged between 50 to 80 years • Ability to tolerate OFF stimulation of up to a period of 14 hours for sleep assessments • Ability to tolerate OFF stimulation of up to 4 hours for pulmonary assessments • Able to attend hospital on up to four separate visits for study duration • Language skills to read, process and communicate the motor, and non-motor aspects of their disease using the questionnaires included in the study protocol • Physical capacity to perform the cardiopulmonary testing • Functional and mental ability to understand the risks of the sleep study and ensure safety to tolerate the overnight sleep study which involves an unfamiliar environment For medically managed PD patients: • Clinical diagnosis of Parkinson’s disease made by a Movement disorder specialist using the Movement Disorder Society criteria • PD symptoms of at least 4 years duration • Male or female sex aged between 50 to 80 years • Able to attend hospital on up to four separate visits for study duration • Language skills to read, process and communicate the motor, and non-motor aspects of their disease using the questionnaires included in the study protocol • Physical capacity to perform the cardiopulmonary testing • Functional and mental ability to understand the risks of the sleep study and ensure safety to tolerate the overnight sleep study which involves an unfamiliar environment For healthy controls: • Male or female sex aged between 50 to 80 years • Able to attend hospital on up to four separate visits for study duration • Language skills to read, process and communicate the motor, and non-motor aspects of their disease using the questionnaires included in the study protocol • Physical capacity to perform the cardiopulmonary testing • Functional and mental ability to understand the risks of the sleep study and ensure safety to tolerate the overnight sleep study which involves an unfamiliar environment
Exclusion criteria
For DBS PD patients: • Pre-existing respiratory diagnosis/dysfunction (i.e. COPD, asthma, interstitial lung disease, pulmonary embolus, obstructive sleep apnoea, pleural effusion, lung malignancy) • Other comorbid conditions likely to contribute to breathlessness (i.e. heart failure, morbid obesity, symptomatic anaemia) • Current smokers • Severe dyskinesia, bradykinesia or tremor OFF stimulation who are likely to not tolerate OFF stimulation • Coexisting cognitive impairment / dementia, defined as Montreal cognitive assessment (MoCA) less than 26, who will not be able to give informed consent or adhere to study protocols with accuracy • Patients under the age of 50 years of age. • Participants who are employees within the researcher’s department including The Perron Institute or the Respiratory department at SCGH For medically managed PD patients: • Pre-existing respiratory diagnosis/dysfunction (i.e. COPD, asthma, interstitial lung disease, pulmonary embolus, obstructive sleep apnoea, pleural effusion, lung malignancy) • Other comorbid conditions likely to contribute to breathlessness (i.e. heart failure, morbid obesity, symptomatic anaemia) • Current smokers • Severe dyskinesia, bradykinesia or tremor OFF stimulation who are likely to not tolerate OFF stimulation • Coexisting cognitive impairment / dementia, defined as Montreal cognitive assessment (MoCA) less than 26, who will not be able to give informed consent or adhere to study protocols with accuracy • Patients under the age of 50 years of age. • Participants who are employees within the researcher’s department including The Perron Institute or the Respiratory department at SCGH For healthy controls: • Pre-existing respiratory diagnosis/dysfunction (i.e. COPD, asthma, interstitial lung disease, pulmonary embolus, obstructive sleep apnoea, pleural effusion, lung malignancy) • Other comorbid conditions likely to contribute to breathlessness (i.e. heart failure, morbid obesity, symptomatic anaemia) • Current smokers • Coexisting cognitive impairment / dementia, defined as Montreal cognitive assessment (MoCA) less than 26, who will not be able to give informed consent or adhere to study protocols with accuracy • Patients under the age of 50 years of age. • Participants who are employees within the researcher’s department including The Perron Institute or the Respiratory department at SCGH
Outcome results
None listed