Neural mechanisms of movement, balance and spatial orientation in health and disease

ISRCTN ISRCTN16535836
DOI https://doi.org/10.1186/ISRCTN16535836
Secondary identifying numbers 1
Submission date
13/10/2016
Registration date
19/01/2017
Last edited
21/09/2023
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
The brain is responsible for controlling balance and orientation in the space around us (spatial orientation). This function allows us to effortlessly walk in busy environments such as a crowded pavement or even to get out of bed at night and walk around in the dark. To achieve such effortless balance, the brain uses information from the vestibular (balance system) and auditory (system for the sense of hearing ) systems in the inner ear, joint and muscle sensors (that help to control limb movement) and what we see. The brain also uses information from previous experience, such as using memories of the layout of the furniture in a room to navigate when we are unable to see in darkness. This study aims to assess how the brain combines these different signals to help our balance in health and disease.

Who can participate?
Adults with brain injury affecting brain functioning and healthy adults of the same age.

What does the study involve?
Participants are invited to attend three hospital appointments over the course of the study, spaced two-three months apart. At each appointment, participants will be assessed by a doctor to check for any changes in health status such as migraine or new onset dizziness. At the visit, participants may undergo an MRI scan, in order to assess how well the central nervous system (the brain and spinal cord) is functioning. In addition, participants complete a number of clinical and behavioural testing that assess the basic mechanisms of nervous functioning that may affect balance (these tests typically occur while seated and include testing of the functioning - and their brain connections - of the inner ear balance and hearing organs, the eye and limb muscles). Finally, patients undergo formal tests of balance which will take place when standing or walking (for safety, patients are either harnessed or accompanied by a researcher). These tests are then repeated three and six months later.

What are the possible benefits and risks of participating?
There are no direct benefits of participating, although the results will provide valuable information for the future development of effective therapies for patients suffering with imbalance and spatial disorientation. There are no notable risks involved with participating.

Where is the study run from?
1. Charing Cross Hospital (UK)
2. St Mary’s Hospital (UK)
3. Hammersmith Hospital (UK)

When is the study starting and how long is it expected to run for?
January 2017 to March 2021

Who is funding the study?
1. Medical Research Council (UK)
2. Imperial College Healthcare Charity (UK)

Who is the main contact?
1. Dr Barry Seemungal (scientific)
b.seemungal@imperial.ac.uk
2. Dr Elena Calzolari (public)
e.calzolari@imperial.ac.uk

Contact information

Dr Barry Seemungal
Scientific

Room 10L14
Charing Cross Hospital
London
W6 8RF
United Kingdom

ORCiD logoORCID ID 0000-0002-6578-0904
Dr Elina Calzolari
Public

10th floor Lab Block
Charing Cross Hospital
London
W6 8RF
United Kingdom

Phone +44 20 331 17042
Email e.calzolari@imperial.ac.uk

Study information

Study designObservational prospective case-control study
Primary study designObservational
Secondary study designCase-control study
Study setting(s)Hospital
Study typeOther
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleAn observational study of the mechanisms contributing to recovery in imbalance and spatial disorientation following injury to the nervous system
Study objectivesStudy aims:
1. To investigate how movement, balance and orientation are impaired in conditions that affect the functioning of the brain
2. To help provide a mechanistic explanation for the future development of therapy in neurological patients with impaired balance and spatial orientation

Hypothesis:
Brain networks coordinate human balance function, and disruption of these networks from disease is important in impairing balance and spatial orientation in humans.
Ethics approval(s)Not provided at time of registration
Health condition(s) or problem(s) studiedBalance, dizziness and spatial disorientation
InterventionAt baseline, participants attend a study visit where they undergo neuroimaging using MRI to assess the structural and functional integrity of the central nervous system. This session will take around an hour.

A series of behavioural and neurophysiological tests (i.e. non-invasive measures of the body’s and brain’s electrical activity and excitability) are also performed either whilst seated or lying down, to assess functions that can affect balance and spatial orientation performance. The tasks include visual, vestibular and auditory stimuli which may require verbal or button press responses. Balance performance will be objectively measured through assessment of body motion during standing and walking tasks. For safety, patients will be tethered or accompanied by a researcher for the standing and walking tests. This testing session will take half a day.

Follow-up will take place at three and six months.
Intervention typeOther
Primary outcome measure1. Functional independence is measured using the Functional Independence Measure (‘FIM’) score at 6 months
2. Cumulative falls over 6 months are measured monthly by reviewing patient diaries either via telephone or by email (or face-to-face during the two follow-up sessions)
Secondary outcome measures1. Central and peripheral vestibular and ocular motor function is measured at baseline, 3 and 6 months
2. Balance is measured using the Romberg coefficient and measures of sway at baseline, 3 and 6 months
3. Neurophysiological markers of recovery are measured using evoked potential amplitudes and latencies and temporo-spatial changes in electrophysiological spectral power at baseline, 3 and 6 months
4. Imbalance and dizziness symptoms are measured using the DHI (dizziness handicap inventory) at baseline, 3 and 6 months
5. Migraine features are measured using IHS criteria (International Headache Society criteria) at baseline, 3 and 6 months
6. Anxiety is measured using the Generalized Anxiety Questionnaire (GAD-7) at baseline, 3 and 6 months
7. Depression is measured using the Patient Health Questionnaire (PHQ-9) at baseline, 3 and 6 months
8. Cognitive function is measured using the Montreal Cognitive assessment, the Mesulam's Cancellation Test, the Line Bisection Test and the Trail Making Test at baseline, 3 and 6 months
9. Blood markers of inflammation are measured from blood samples collected at baseline, 3 and 6 months
10. White and grey matter and whole brain functional connectivity are measured using MRI scanning at baseline, 3 and 6 months
Overall study start date01/01/2017
Completion date01/03/2021

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit75 Years
SexBoth
Target number of participants225 (includes patients and controls)
Key inclusion criteriaPatients
1. Injury to the brain and its sensorium (including eyes, ears, proprio-somatosenory system) from trauma, inflammation and/or disturbed vascular supply
2. Age 18-75
3. Male or Female

Controls
1. Healthy individual
2. Age 18-75
3. Male or Female
Key exclusion criteriaPatients
1. Premorbid acute or chronic medical condition that might impair balance and/or spatial orientation (e.g. previous peripheral or central vestibular disturbances)
2. Premorbid active psychiatric, neurological or neuro-otological condition
3. Premorbid substance abuse

Controls
1. Chronic medical condition requiring drug therapy (healthy controls with a past history of migraine in remission will be admissible)
2. Premorbid acute or chronic medical condition that might impair balance and/or spatial orientation (e.g. previous peripheral or central vestibular disturbances)
3. Premorbid active psychiatric, neurological or neuro-otological condition
4. Premorbid substance abuse
Date of first enrolment01/03/2017
Date of final enrolment01/03/2020

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
St Mary’s Hospital
Praed Street
London
W2 1NY
United Kingdom
Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom

Sponsor information

Imperial College Healthcare NHS Trust
Hospital/treatment centre

Joint Research Compliance Office
Room 21
Medical School
St Mary's Campus
London
W2 1NY
England
United Kingdom

Website http://www.imperial.nhs.uk/
ROR logo "ROR" https://ror.org/056ffv270
Imperial College London
University/education

Joint Research Compliance Office
Room 215
Medical School
St Mary's Campus
London
W2 1NY
England
United Kingdom

Funders

Funder type

Research council

Medical Research Council
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom
Imperial College Healthcare Charity

No information available

Results and Publications

Intention to publish date01/06/2021
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPublications in peer reviewed journals - open access.
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request from barseem@gmail.com.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Other publications 14/10/2022 21/09/2023 Yes No
Results article 15/12/2022 21/09/2023 Yes No
Results article 01/01/2021 21/09/2023 Yes No

Editorial Notes

21/09/2023: Publication references added.
09/02/2017: Internal review.