DBS and Respiration

Deep Brain Stimulation in Parkinson's Disease: Respiratory Testing

Patients referred to neurosurgery routinely and safely undergo deep brain stimulation (DBS) for treatment of neurological conditions, most commonly Parkinson's disease.

The investigators have observed that respiratory problems (breathlessness) sometimes occur subsequent to DBS of the subthalamic nucleus (STN). This study aims to determine whether this is indeed a consequence of STN stimulation. Secondary objectives include identification of the respiratory physiological mediators of any interoceptive neuromodulation observed, changes in daily physical activity and MRI structural connectivity analysis.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: DBS

Detailed Description

A continuous cohort of Parkinson disease patients planned to undergo STN-DBS will be approached to participate in this study (i.e. every patient will be offered participation in the study). Over the same time period other DBS patients (GPi and VIM) will be approached before their implantation procedure to participate as controls/comparators. Participants will all be offered the full study, but will also be free to participate in a smaller number of activities if so chosen.

Patients will be assessed both pre-operatively and post-operatively where they will complete a compound respiratory questionnaire and tests of respiratory interoception and function. Post-operatively, these tests will be carried out with stimulation ON and OFF, the order of which will be randomised between patients.

Data on daily activity will be collected during pre- and post-operative windows, using a wearable pedometer/heart-rate monitor.

Positive findings of respiratory neuromodulation will be correlated between patients with structural connectivity (e.g. STN-insula.) from pre-operative MRI scans.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Alex Green, FRCS; Phone Number: +44 01865227645; Email: alex.green@nds.ox.ac.uk

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • John Radcliffe Hospital
      • Contact: Alex Green, FRCS; Phone Number: 01865234762; Email: alex.green@nds.ox.ac.uk

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

STN (Parkinson's disease) GPi (movement disorder, control) VIM (movement disorder, control)

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study.
• Male or female, aged 18 years or above.
• Planned for required DBS surgery
• Fluent in the English language
• For experimental group: diagnosed with Parkinson's disease

Exclusion Criteria:

• Female who is pregnant
• Subject is currently participating in a clinical investigation that includes an active treatment arm which may affect the respiratory system.
• Acute respiratory problem at time of experimental session: e.g. rhinosinusitis, pharyngitis, asthma exacerbation

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
STN DBS; Patients planned to undergo deep brain stimulation of the subthalamic nucleus	Device: DBS; Patients are tested pre-operatively and the post-operatively with their implanted neurostimulators ON and OFF. DBS implantation itself is part of routine care, and not part of the study.
GPi DBS; Patients planned to undergo deep brain stimulation of the globus pallidus interna	Device: DBS; Patients are tested pre-operatively and the post-operatively with their implanted neurostimulators ON and OFF. DBS implantation itself is part of routine care, and not part of the study.
VIM DBS; Patients planned to undergo deep brain stimulation of the ventral intermediate nucleus of thalamus.	Device: DBS; Patients are tested pre-operatively and the post-operatively with their implanted neurostimulators ON and OFF. DBS implantation itself is part of routine care, and not part of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in breathlessness	Dyspnoea questionnaire (D12, MRC)	Pre-operatively and post-operatively (6-months)
Change in breathlessness	Breathlessness ratings (modified-Borg Scale) from experimentally induced breathlessness. 0 = none, 10 maximum. Reported every 15 seconds.	ON and OFF stimulation between 1 and 6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary function	Spirometry	ON and OFF stimulation between 1 and 6 months after surgery
Change in airways resistance	Oscillometry	ON and OFF stimulation between 1 and 6 months after surgery
Change in respiratory muscle strength	Maximum inspiratory/expiratory pressures	ON and OFF stimulation between 1 and 6 months after surgery
Change in surface electromyography of respiratory muscles	Signal analysis for evidence of tremor	ON and OFF stimulation between 1 and 6 months after surgery
Change in hypercapnic ventilatory response	Changes in ventilation from incrementally increased inhaled CO2	ON and OFF stimulation between 1 and 6 months after surgery
Change in breath-hold	Dyspnoea threshold and breakpoint	ON and OFF stimulation between 1 and 6 months after surgery
Change in daily activity	Pedometry	Pre-operatively (10 days) and post-operatively (10 days, within 6 months of surgery once recovered from surgery and programmed)
Change in daily activity	Heart rate	Pre-operatively (10 days) and post-operatively (10 days within 6 months of surgery once recovered from surgery and programmed)
MRI structural connectivity	DTI correlation with respiratory outcomes	Pre-operative scan with post-operative analysis through study completion at an average of 1 year

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Oxford Brookes University
• Investigators: Principal Investigator: Alex Green, FRCS, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): July 21, 2024
• Study Completion (Estimated): September 21, 2024

Study Registration Dates

• First Submitted: July 18, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson disease; respiratory; dyspnea; dyspnoea; breathlessness; movement disorder
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 256825

Drug and device information, study documents

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