Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05809973 |
| Other study ID # |
StrokeVIS |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 15, 2021 |
| Est. completion date |
March 31, 2024 |
Study information
| Verified date |
March 2023 |
| Source |
Oslo University Hospital |
| Contact |
Anne Hege Aamodt, MD, PhD |
| Phone |
+4791502770 |
| Email |
a.h.aamodt[@]medisin.uio.no |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Longitudinal, prospective, single-center observational study of visual impairment after
stroke.
Population: Patients admitted with acute ischemic stroke at the Regional Stroke Unit at Oslo
University Hospital who are assessed to not have more serious neurological deficits than to
be eligible for a prospective observational study of visual impairment. National Institute of
Health Stroke Scale (NIHSS) will be used for screening of the patients eligible for the study
with cut off of NIHSS 20. Based on the number of patients admitted to our center to include
120 patients in the StrokeVIS study.
The study aims are:
1. To determine the prevalence of visual impairment in stroke patients in the acute phase
and after 3 months.
2. To compare visual impairment in those treated with EVT and those not.
3. To determine the sensitivity and specificity of the Vision Screening Assessment (VISA)
tool for detection of visual impairment in stroke patients.
4. To assess possible association between brain MRI lesions and visual impairment in stroke
patients in the acute phase.
6) To assess any cognitive deficits at 3-month follow-up that could impact visual function.
Inclusion criteria:
1. Acute ischemic stroke and NIHSS < 20
2. Age ≥18 years.
3. Written informed consent of the patient or oral informed consent witnessed by a doctor.
Exclusion criteria:
1. NIHSS < 20
2. No willingness and ability of the patient to participate in all baseline and follow-up
examinations.
Duration of study participation: 3 months.
Description:
1. Introduction Stroke is the second leading cause of death and a leading cause of
disability worldwide (1). Each year in Norway there are approximately 12,000 incidences
of stroke, resulting in tremendous health-related and economic consequences (2). In
recent years, endovascular intervention (EVI) (Fig 1) has revolutionised the treatment
of stroke caused by occlusion of the internal carotid or proximal segment of the middle
cerebral artery (3). The degree of benefit is profound, with a number needed to treat
(NNT) as low as 2.5, resulting in one patient with reduced disability (4, 5). Few, if
any, therapies in medicine can obtain a similar level of benefit.
The Regional Stroke Unit at Oslo University Hospital has 400 acute stroke patients every
year with approximately 250 patients treated with EVT each year. The treatment of this
group of stroke patients is characterized by advanced imaging and intervention; close
clinical monitoring in a specialized stroke unit and interdisciplinary rehabilitation
(6-8).
Figure 1. Schematic representation of stroke due to large vessel occlusion and infarct
zone distal to the occlusion (upper right). In endovascular intervention, the catheter
is passed through the blood vessels from the groin to the brain and the blood clot "is
expelled (upper left and lower).
Vision is the most complex sense in humans with a multifaceted interaction between the
eyes and the brain. Studies have shown that up to 60% of stroke patients have some form
of visual impairment (9); in Norway alone, it is estimated that approximately 30,000
people live with different visual impairments following a stroke. Among vision
impairments, we estimate that 20-30% is due to visual field outcomes (9). An equally
large proportion (30-40%) is comprised of various forms of visual neglect, where
attention to visual impressions is impaired (10, 11). Other common visual impairments
after stroke are double vision, focusing problems and light sensitivity (Fig 2).
Figure 2. Among the visual impairment after stroke, it is estimated that 20-30% is due
to visual field outcomes (upper right). An equally large proportion (30-40%) is made up
of various forms of visual neglect, where attention to visual impressions is diminished
(lower right). Other common visual impairments after stroke are double vision (upper
right), focusing problems, visual impairment and hallucinations (lower right).
In the annual report of the Norwegian Stroke Register from 2018, only 17.4% of stroke
patients were registered with visual impairment (12). This figure is lower than expected
and indicates a significant under-reporting and/or underdiagnosis. Misinterpretation of
symptoms due to dysphasia, cognitive or motor difficulties can lead to underdiagnosis
(Wilhelmsen 1994, 2003; Zihl 2000). It is also conceivable that underdiagnosis of visual
impairment at dedicated stroke units is due to the lack of both good screening tools,
and neuro-ophthalmological expertise. These disciplines are more closely connected to
eye departments rather than neurological departments. Unfortunately, stroke patients may
be discharged from stroke units without visual impairment being recognised (13, 14).
This increases the risk of injury and accidents, prevents early rehabilitation and
reduces the quality of life. Considering this, it is clear that there is a great need
for an interdisciplinary research project focusing on visual impairment after stroke in
Norway. This is further emphasised by a newly established multidisciplinary network,
NorVIS, which focuses solely on vision problems after stroke. The network is supported
by funding from the Research Council of Norway and is led by Professor Helle Falkenberg
at the University of Southeast Norway (www.usn.no).
It is well documented that rapid stroke rehabilitation provides a better level of
function, especially in motor deficits (15). For patients with visual impairment,
similar documentation is lacking (15). Knowledge of the brain's plasticity and potential
for targeted rehabilitation motivates a project that examines visual impairment after
stroke with the goal of improving visual rehabilitation for patients. It is worth noting
the importance of early intervention in post-stroke sequela; if visual impairment is
discovered at a later stage, it is conceivable that the effect of visual rehabilitation
will be reduced. The problem of underdiagnosis must be addressed, and an overarching
goal, for all stroke patients, is to assess their visual function in the acute setting.
A well-validated screening study of stroke patients and a more specialised examination
of them the screening study gives reason to suspect vision problems. Cooperation between
stroke units, eye departments, vision educators in municipalities and assistive
technology centres should also be organised in an appropriately to insure correct follow
up at home in the form of specialised rehabilitation.
2. Study objectives
The study aims are:
1. To determine the prevalence of visual impairment in stroke patients in the acute phase
and after 3 months.
2. To compare visual impairment in those treated with EVT and those not.
3. To determine the sensitivity and specificity of the Vision Screening Assessment (VISA)
tool for detection of visual impairment in stroke patients.
4. To assess possible association between brain MRI lesions and visual impairment in stroke
patients in the acute phase.
6) To assess any cognitive deficits at 3-month follow-up that could impact visual function.
3. Methods - study design, study population: Study design: Longitudinal, prospective,
single-center observational study.
Population: Patients admitted with acute ischemic stroke at the Regional Stroke Unit at Oslo
University Hospital who are assessed to not have more serious neurological deficits than to
be eligible for a prospective observational study of visual impairment. National Institute of
Health Stroke Scale (NIHSS) will be used for screening of the patients eligible for the study
with cut off of NIHSS 20. Based on the number of patients admitted to our center to include
120 patients in the StrokeVIS study.
Inclusion criteria:
1. Acute ischemic stroke and NIHSS < 20
2. Age ≥18 years.
3. Written informed consent of the patient or oral informed consent witnessed by a doctor.
Exclusion criteria:
1. NIHSS < 20
2. No willingness and ability of the patient to participate in all baseline and follow-up
examinations.
4. Study procedure and assessments, flowchart
Duration of study participation: 3 months.
Plan for progress Inclusion period: 24 months Duration of follow-up period: 3 months.
Inclusion of patients will start in November 2021. Clinical assessment
Visual examination at baseline and after 3 months:
1) Best-corrected visual acuity for distance and near, reading ability 2) Automated perimetry
with the monocular Esterman program, alternatively confrontational visual field examination
for patients who are unable to perform perimetry 3) Ocular motility 4) Visual attention and
perception 6) Direct ophthalmoscopy 7) National Institute of Health Stroke Scale
The patients will be invited to participation by the treating physician in the stroke unit.
In case of aphasia and other conditions that makes the patient unable to give informed
consent their relatives will be informed about the study and given the invitation for
participation. A patient can also consent to inclusion if informed consent is inferred as
witnessed by a medical practitioner.
An experienced orthoptist and neurologist will perform the abovementioned examinations. In
addition, an independent researcher will collect data using the VISA tool. At the 90 day
control, the VISA tool will be administered by a neurologist. Clinical neurological deficits
as well as functional level, both premorbid and at discharge, will be recorded with Modified
Rankin Scale (mRS).
The neuro-ophthalmological examinations define the true positive and negative findings and
makes it possible to validate the VISA tool. The results of the neuro-ophthalmological
examination and VISA tool are blind to each other.
Subgroups of patients will be well defined according to treatment during the acute stroke.
Conservative treatment vs active treatment with trombolysis and/or mechanical thrombectomy.
There will also be subgroups according to ability to undergo full neuro-ophthalmic testing vs
those who are partially able to complete the full test battery.
Patients with visual impairment will be invited to the 90-day follow-up and they will again
complete the neuro-ophthalmic examination and the VISA tool.
EQ-5D-3L (EuroQoL Health Questionnaire to measure general health. EQ-5D-3L contains 5
questions on physical function, pain and anxiety/depression with 3 graded response options
and has been used in different diseases inter-nationally as well as in Norwegian setting
(17). We selected EQ-5D as a generic instrument due to brevity (5 items). This tool is widely
used in PROM studies internationally due to the feature of measuring QALY (quality-adjusted
life years) the burden of a disease, which will be utilized in future economic evaluations of
the treatment.
MOCA (Montreal cognitive assessment) will be performed at the 90 day follow-up to determine
if patients have any cognitive deficits that can influence the neuro-ophthalmic examination
and the VISA screening tool.
VISA (Visual Impairment Screening Tool) This is a validated screening tool currently in use
in the UK to simplify and increase the detection of visual impairment in patients with acute
stroke. Our project will use a Norwegian translation of the tool which has been approved by
the developer.
Brain MRI Brain MRI is routinely taken in these patients post EVT (approximately 24 hours).
Magnetic Resonance Imaging (MRI) is a superior imaging modality for early detection of
cerebral ischemia, infarction, hemorrhage and brain edema. MRI provide reliable information
on three key components of stroke physiology: 1) the presence and location of an
intravascular thrombus which can be treated with thrombolysis and/or MT; 2) the presence and
size of irreversibly ischemic tissue; and 3) the presence and extension of hypoperfused
tissue at risk for subsequent infarction unless adequate perfusion is restored (salvageable
brain tissue) (18). All this information, required to extend the therapeutic window, improve
treatment outcome and minimize the risk of intracerebral hemorrhage (ICH) can be obtained by
using a multimodal MRI protocol.(18) (intracranial time-of-flight magnetic resonance
angiography (MRA); diffusion-weighted imaging (DWI), T2-weigted fluid-attenuated inversion
recovery (T2-FLAIR), susceptibility weighted imaging (SWI) and perfusion-weighted imaging
(PWI) using dynamic susceptibility-weighted contrast-enhanced sequences (1.5 Tesla MR
scanner, Siemens, Erlangen, Germany). MRI Scans are performed at baseline for the selection
of patients for acute reperfusion therapy in extended time windows, and in patients in which
time of stroke onset is unknown. Control MRIs are done at 24±6 hours in patients without
contraindications and CT is done in the remainder.
Statistical methods The main analysis is planned when all patients have concluded the study,
all data has been entered, verified and validated, and the database has been locked. The
primary analysis will be performed on the intention-to-treat population. The primary endpoint
and dichotomous secondary endpoints will be analyzed using logistic regression models,
adjusted for strong prognostic factors at baseline. Continuous secondary variables will be
analysed using analysis of covariance (ANCOVA). Missing data for the primary endpoint will be
imputed with worst outcome.
5. Plan for milestones, dissemination and publishing The overall project plan is designed to
ensure an efficient workflow and stable progress throughout the study period. The study will
be registered at www.clinicaltrials.gov, Helsenorge.no and be presented at national and
international meetings and congresses. After the follow-up phase has been completed, the
results will be analyzed and the manuscript with the primary endpoints prepared within 6
months.
- Autumn 2021 - Autumn 2023: Recruitment of patients and conducting neuro-ophthalmological
screening + VISA in 100 patients.
- Autumn 2023 - Spring 2024: Processing and analysis of data. Publication in international
peer reviewed journal.
- Autumn 2023: Media Campaign: "Vision into stroke management: PRATE-SMILE LØFTE OG SE"
StrokeVIS´ early priorities will be to develop a dissemination and communication plan. A
media strategy consisting of dissemination through social media and mainstream media will be
developed together with user representatives from the Norwegian Heart and Lung Patient
Association and the Norwegian Association of the Blind and Partially Sighted and the user
representative panel, Division of Clinical Neuroscience at OUH. As members of the Norwegian
Brain Council, information will also be distributed to the public through their information
channels. The scientific community will be targeted through publications in international
peer-reviewed journals. The study will be presented at with scientific meetings, including
ESOC 2023, and American Academy of Neurology 2023. We will also give lectures together with
representatives from the Norwegian Heart and Lung Patient Association and the Norwegian
Association of the Blind and Partially Sighted, and utilise this experience in the
dissemination of the current project at a national level. The demonstration of better
management of visual impairment in stroke will have considerable clinical impact in the
health care of these patients. After the publication of the results, we will take the
initiative for better information regarding visual impairment in stroke.
6. Funding StrokeVIS is an investigator driven academic study and will be run by a PhD
student, study nurse and orthoptist at Oslo University Hospital The project is financed
through a grant from the Norwegian Association of the Blinded and Partially sighted (Norges
Blindeforbund).
User interaction The project has considerable user interaction. The project concept has been
discussed both with the User panel for the Division of Clinical Neuroscience. Their input has
been included in the planning of the project, especially in relation to study design and the
coordination of other stroke studies, as well as to describe project impact. Representative
for the Division of Clinical Neuroscience user panel will be part of the project steering
committee. We will arrange a start-up meeting and annual project meetings for the steering
committee and all active research personnel in the project. In the start-up meeting, the
practical implementation of the research protocol for both the hospital, specialist clinic
and the patients will be the focus. In the annual project meetings, continuous evaluation of
the project will be performed.
7. Study organization, roles and cooperation Study group Anne Hege Aamodt, Dep of Neurology,
Oslo University Hospital, University of Oslo, Stephen J Ryan, Dep of Neurology, Oslo
University Hospital, University of Oslo, orthoptist (to be recruited), Dep of Ophthalmology,
Oslo University Hospital, University of Oslo, Morten C. Moe PhD, Professor, Clinic Head of
Research Clinic for Head, Neck and Reconstructive Surgery and Academic Chair at Dep. of
Ophthalmology, Retinal Consultant (Leading Ophthalmologist), co-supervisor for the PhD
student, Øystein Kalsnes Jørstad, Dep. of Ophthalmology, Neuro-ophthalmologist, co-supervisor
for the PhD student. Study nurse (to be recruited), Dep of Neurology, Oslo University
Hospital. Arild Hagen, the Norwegian Heart and Lung Patient Association and the Norwegian
Association of the Blind and Partially Sighted.
Collaborators Fiona Rowe, Professor of orthoptics, Health Services Research, University of
Liverpool, England, Helle Falkengberg: Professor, University of South-Eastern Norway,
National centre for vision, optics and eye health, Faculty of health- and social sciences,
Kongsberg, Norway.
Hospital (OUH):
Dep of Ophthalmology: is a large ophthalmology department even in European terms; it has a
total staff of 220 people, including 70 physicians, ten operating theatres, and a ward of 19
beds. The department has a close collaboration with all other participating ophthalmological
departments through a common email-list for updates and discussions, and representatives from
all departments meet annually through the Norwegian ophthalmological society.
Dep of Neurology, Stroke Unit: A large neurology department with outpatient clinic,
laboratories and wards at both Ullevål and Rikshospitalet. The department has 8
professorships in neurology and one in clinical neurophysiology. The department has a large
research activity on cerebrovascular disorders, headache, movement disorders, epilepsy,
multiple sclerosis, vertebrogenic diseases and neuropathies.
Dep of radiology: A large radiology department with laboratories at both Ullevål and
Rikshospitalet. The department has 7 professorships in radiology and a large research
activity.
The Department of Neurology and Radiology have built up EVI service during the last 15 years
using a coordinated multidisciplinary team.
10. Data management plan Quantitative data collected in a database. A specific database
management protocol will be developed. The main investigator is responsible for transferring
data to the database. A study nurse is responsible for controlling the transfer of source
data to the database to ensure the quality of data transferal. The database is password
protected and unavailable to non-study personnel. All data are stored de-identified with an
individual code for each participant in the OUH secure research server, accessible only to
specified study personnel. The code list is kept on a separate code list.
11. Ethical considerations The project will aim at the highest ethical standards. The study
will not start until the Norwegian South-Eastern Regional Ethical Committee (EC) has approved
this project. Informed written consent signed by the patient, verbal consent from the
patients as witnessed by a non-participating health care person or consent by the signature
of the patient's family will be obtained before inclusion in the study. Any amendment or
modification to the protocol will be sent to the EC for approval and every effort will be
taken to ensure the accuracy and reliability of data. No personal identification of study
subjects will be possible for other researchers than the project leader and other clinicians
directly involved in data collection. The study does not involve harm or risk to the
participants, except possible minor pain related to blood samples. This study will be carried
out in accordance with Norwegian and international standards for medical research as
described in the Declaration of Helsinki concerning medical research in humans (59th WMA
General Assembly, Seoul, October 2008). The protocol will also be registered in
clinicaltrials.gov and at "helsenorge.no".
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