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 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 design	Observational prospective case-control study
Primary study design	Observational
Secondary study design	Case-control study
Study setting(s)	Hospital
Study type	Other
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	An observational study of the mechanisms contributing to recovery in imbalance and spatial disorientation following injury to the nervous system
Study objectives	Study 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) studied	Balance, dizziness and spatial disorientation
Intervention	At 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 type	Other
Primary outcome measure	1. 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 measures	1. 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 date	01/01/2017
Completion date	01/03/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	Both
Target number of participants	225 (includes patients and controls)
Key inclusion criteria	Patients 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 criteria	Patients 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 enrolment	01/03/2017
Date of final enrolment	01/03/2020

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"	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 date	01/06/2021
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Publications in peer reviewed journals - open access.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from barseem@gmail.com.

Study outputs

Output type	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.