Deep Brain Stimulation for Autonomic and Gait Symptoms in Multiple System Atrophy

NCT03593512 | Completed DMC

• 1 other identifier: 13340
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Patients referred to neurosurgery routinely and safely undergo deep brain stimulation (DBS) for treatment of symptoms related to neurodegenerative conditions, most commonly Parkinson's disease. In the investigators experience, and published evidence shows, that stimulation has effects on the autonomic nervous system. In patients undergoing therapeutic DBS for a particular subtype of Parkinsonism, Multiple System Atrophy, the further effects on autonomic parameters such as blood pressure and bladder symptoms as well as the originally intended indications (gait and movement disorder) will be investigated. The mechanisms of any effects will also be studied by using a number of techniques such as magnetoencephalography (MEG) and Muscle Sympathetic Nerve Activity (MSNA) recording. Key goals are to:

1. 1.Demonstrate that stimulation of the peduculopontine nucleus (PPN) improves autonomic function and has an attendant improvement on patients' quality of life
2. 2.Investigate the role of the PPN and how it interacts with other brain areas.

Conditions

Multiple System Atrophy; Autonomic Failure; Postural Hypotension; Bladder, Neurogenic; Gait Disorders, Neurologic

Keywords

multiple system atrophy; autonomic

Outcome Measures

Primary Outcomes (4)

• EuroQol 5 Dimension (5 level) score before and after deep brain stimulation

  Measurement of quality of life before and after surgery. Results will be given as description of health states - it is not quantitative.

  Through study completion, but on average, over an 8 month period for each patient

• Fluency of gait as measured by accelerometry before and after deep brain stimulation

  Measurement of gait parameters before and after surgery

  Through study completion, but on average, over an 8 month period for each patient

• Modified composite autonomic symptom scale before and after deep brains stimulation

  Measurement of autonomic symptomatology before and after surgery - Score from 0-100

  Through study completion, but on average, over an 8 month period for each patient

• Change in postural blood pressure change before and after PPN DBS

  Measurement of effect on postural blood pressure change before and after surgery

  Through study completion, but on average, over an 8 month period for each patient

Secondary Outcomes (4)

• Number of Participants With Treatment-Related Adverse Events as Assessed by using approved UK reporting procedure

  Through study completion, 2 years

• Muscle sympathetic nerve activity before and after deep brain stimulation

  Through study completion, but on average, over an 8 month period for each patient

• Cortical magentoencephalography profile with deep brain stimulation on and off

  3-6 months after surgery

• Physical anatomical white matter connections between the pedunculopontine nucleus and the rest of the central nervous system

  Before surgery and 3-6 months after surgery

Study Arms (1)

PPN DBS

EXPERIMENTAL

All patients will undergo bilateral PPN DBS

Procedure: Deep brain stimulation

Interventions

Deep brain stimulation PROCEDURE

Bilateral deep brain stimulation of the pedunculopontine nucleus

PPN DBS

Eligibility Criteria

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

You may qualify if:

• Diagnosis of MSA with disabling autonomic symptoms (bladder dysfunction and orthostatic symptoms
• UMSARS score of \>40
• \>6/12 in the autonomic subsection (Q9-12) of the UMSAR scale
• Patient willing and able to give informed consent to involvement in the study.
• Male or female, aged 18 years or over.
• Able to walk unaided (to perform gait analysis)
• Have an anticipated prognosis \> 2 years

You may not qualify if:

• The patient is unwilling to participate or unable to give informed consent.
• The patient has been deemed unfit for stimulator insertion by their healthcare team i.e. surgical contraindications to DBS:
• Bleeding or coagulation disorder
• Not fit for general anaesthetic
• Unable to deal with implanted DBS system (turn on and off and recharging where applicable, although it is acceptable if a carer can do this)
• Untreated anxiety or depression
• Unable to undergo MRI (eg. metal implants)
• Subject is currently participating in a clinical investigation that includes an active treatment arm.
• Female who is pregnant - testing will be offered to female patients who are unsure.

Sponsors & Collaborators

• University of Oxford: lead
• Medical Research Council: collaborator

Study Sites (1)

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Multiple System Atrophy; Pure Autonomic Failure; Hypotension, Orthostatic; Urinary Bladder, Neurogenic; Gait Disorders, Neurologic

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Orthostatic Intolerance; Hypotension; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Alex L Green, FRCS(SN)

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Evaluation of symptomatology before and after implantation of DBS electrodes; followed by cross-over of "on" and "off" stimulation

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: July 20, 2018
• Study Start: September 9, 2018
• Primary Completion: December 1, 2021
• Study Completion: August 8, 2022
• Last Updated: November 2, 2022

Record last verified: 2022-05

Locations

GB (1)