Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Barry Seemungal
ORCID ID
http://orcid.org/0000-0002-6578-0904
Contact details
Room 10L14
Charing Cross Hospital
London
W6 8RF
United Kingdom
Type
Public
Additional contact
Dr Elina Calzolari
ORCID ID
Contact details
10th floor Lab Block
Charing Cross Hospital
London
W6 8RF
United Kingdom
+44 20 331 17042
e.calzolari@imperial.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1
Study information
Scientific title
An observational study of the mechanisms contributing to recovery in imbalance and spatial disorientation following injury to the nervous system
Acronym
Study hypothesis
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
Not provided at time of registration
Study design
Observational prospective case-control study
Primary study design
Observational
Secondary study design
Case-control study
Trial setting
Hospitals
Trial type
Other
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Drug names
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 trial start date
01/01/2017
Overall trial end date
01/03/2021
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
225 (includes patients and controls)
Participant 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
Recruitment start date
01/03/2017
Recruitment end date
01/03/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
Trial participating centre
St Mary’s Hospital
Praed Street
London
W2 1NY
United Kingdom
Trial participating centre
Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom
Sponsor information
Organisation
Imperial College Healthcare NHS Trust
Sponsor details
Joint Research Compliance Office
Room 21
Medical School
St Mary's Campus
London
W2 1NY
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Organisation
Imperial College London
Sponsor details
Joint Research Compliance Office
Room 215
Medical School
St Mary's Campus
London
W2 1NY
United Kingdom
Sponsor type
University/education
Website
Organisation
Imperial College Healthcare NHS Trust
Sponsor details
Sponsor type
Not defined
Website
Funders
Funder type
Research council
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Funder name
Imperial College Healthcare Charity
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
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.
Intention to publish date
01/06/2021
Participant level data
Available on request
Basic results (scientific)
Publication list