Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03259178 |
| Other study ID # |
ConBVT |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 8, 2017 |
| Est. completion date |
March 1, 2018 |
Study information
| Verified date |
March 2019 |
| Source |
McGill University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Sports-related concussion affect 1.6 to 3.8 million people each year in the United States.
Despite increased media attention and awareness campaigns, the exact number is difficult to
determine due to underreporting by athletes. The types of symptoms experienced with a
concussion depend on the area of the brain that was affected. The most frequent symptoms
include: headaches, cognitive difficulties, dizziness, neck pain, visual disturbances,
difficulty sleeping, and fatigue.
Despite the availability of many treatment options, some patients continue to experience many
symptoms - such as headaches, dizziness, visual disturbances, balance problems, sensitivity
to light, and difficulties concentrating - that negatively affect school, work, and quality
of life for long periods of time. All of these symptoms are similarly experienced by
individuals with visual dysfunctions, such as the inability of the eyes to move together.
This finding has led some to recommend a visual component in concussion management.
Therefore, the purpose of this study is to determine whether changes in the results of 7
binocular vision tests (BVT) over time in patients with concussion correlate with changes in
concussion symptoms. The investigators will measure 46 concussion patients aged 18 to 30
years with each of these tests and assess their concussion symptoms on up to four separate
visits, which depend on when the patient's symptoms improve.
The tests the investigators will evaluate measure: 3D vision, uniform movement of the eyes,
ability of the eyes to adapt to a target moving towards and/or away from the eyes, quick
movements of the eyes, natural alignment of the eyes, and double vision as a target is moved
towards the eyes. In addition, concussion symptoms will be measured by a standardized
concussion questionnaire (SCAT3) at each visit.
The results of each BVT will be entered into a statistical model with the participant's
concussion symptom score to determine if there is an association between the change in
symptoms and the change in the results of the tests.
Description:
Sports-related concussion affect 1.6 to 3.8 million people each year in the United States.
Despite increased media attention and awareness campaigns, the exact incidence is difficult
to determine due to underreporting by athletes. Concussion is defined as a set of
pathological reactions leading to direct damage of the brain, which may occur from a direct
or indirect blow to the head. The types of symptoms experienced depend on the area of the
brain that was affected. The most frequent symptoms include: headaches, cognitive
difficulties, dizziness, neck pain, visual disturbances, difficulty sleeping, and fatigue.
Despite the availability of many treatment options such as neurological and psychological
tests, some patients continue to experience many symptoms - such as headaches, dizziness,
visual disturbances, balance problems, sensitivity to light, and difficulties concentrating -
that negatively affect school, work, and quality of life for long periods of time. All of
these symptoms are similarly experienced by individuals with visual dysfunctions such as
dysfunctions of binocular function or convergence insufficiency. This finding has led some to
recommend a visual component in concussion management. Therefore, the purpose of this study
is to determine if changes in the results of 7 binocular vision tests (BVT) over time in
patients with concussion correlate with changes in concussion symptoms.
The investigators will measure 46 concussion patients with each of these tests and the SCAT3
on up to 4 separate milestone time points as described below:
- M1 = baseline; as soon as possible after recruitment
- M2 = when participants qualitatively feel that their concussion symptoms have
"significantly improved"
- M3 = when participants are symptom-free at with activity for 1 week, or at 3 months
post-enrolment in the study, whichever comes first. This milestone will also be the last
measurement and mark the end of their participation.
- M* = Participants who do not have significant improvement (i.e. M2) within 2 weeks of
baseline testing will also be tested at the 2-week mark. They will still be tested at
both M2 and M3.
Demographic information relevant to the study will be collected in order to appropriately
describe the population and evaluate the potential effect modification of these factors on
the observed correlations. Demographic variables to be recorded include: age, sex, highest
level of education achieved, the use of corrective lenses for vision problems, occupation,
any relevant past medical history (i.e. migraines, vision problems, medication, etc.), the
main sports activity the athlete is involved in, and the last of activities that the athlete
will be returning to after healing, with an emphasis on high risk activities for concussions.
Furthermore, information relevant to the concussion event will be recorded to characterize
the injury. This includes information regarding the accident resulting in concussion,
activity at the time of injury, and the mechanism of injury (the presence or absence of head
contact is important).
Participants will complete the symptom portion (section 3) of the validated SCAT3 form that
is part of the accepted standard for management of concussion. The symptoms listed are:
headache, "pressure in head", neck pain, nausea or vomiting, dizziness, blurred vision,
balance problems, sensitivity to light or noise, "feeling slowed down", feeling like "in a
fog", "don't feel right", difficulty concentrating, difficulty remembering, fatigue or low
energy, confusion, drowsiness, trouble falling asleep, more emotional, irritability, sadness,
nervous or anxious. Symptoms are scored on a scale of 0 (none) to 6 (severe). The overall
symptom score is the sum of all individual symptom scores.
The investigators will include an additional seven questions about symptoms - that are asked
by some clinicians: "Symptoms worse with physical activity", "Symptoms worse with mental
activity", "Motion sickness", "Discomfort while reading", "Discomfort while using a
computer", "Double vision", "Pain behind your eyes". Each symptom is again scored between 0
(none) to 6 (severe).
BVTs will be examined, which differ from optometry tests in that they use more advanced
equipment which can measure very small deviations in several domains of the visual system.
These BVT measure various elements of the visual system and will be described in detail
below:
1. Gross stereoscopic acuity: (range 0 - 15 arc seconds) Our binocular vision allows us to
see in three dimensions (3D), or more simply, to perceive depth. In this tests, seated
participants wearing 3D glasses are shown images. Inability to see depth or in 3D will
cause the images to appear as points instead of raised objects. The objects are
presented in different stages, with each stage requiring participants to discriminate
different levels of depth perception. The test is scored in optical units - ranging from
0 to 15 arc-seconds. The maximum score corresponds to the level where the last object
was identified.
2. Convergence measured by "motor punctum proximum": (cm) When an object is moving towards
our eyes, they symmetrically converge in order to maintain focus. There is, however, a
point at which our eyes no longer symmetrically converge, which is referred to as the
point of convergence or "motor punctum proximum". This test measures the distance (cm)
between the bridge of the nose and the point of convergence in seated participants as an
object is moved closer to their head.
3. Convergence fusional proximum: (diopters, prism convergence units) This test is similar
to (2). When an object is moving closer to our head, our eyes symmetrically converge to
maintain focus. However, when the object is moved beyond the participant's ability
converge, the participant will begin to see two images (double vision). This test
measures the distance between the bridge of the nose and the point where double vision
(cm) occurs in seated participants as an object is moved closer to their head.
4. Binocular fusion with convergence: (diopters, prism convergence units) This test
measures how well a participant can adapt to challenges in focusing light on the retina.
This measure is comprised of two almost identical tests - differing only by distance.
One test occurs when an object placed at 3m from the seated participant, and the other
with an object placed at 30cm from the seated participant. Light from the object is
passed through a prism - this is analogous to moving the object further from the body.
In response, the eyes must diverge (separate) to focus on the object, just as they would
if the image actually moved away from the body. Different prisms are used to create
increasing challenges for the participants. The score for these tests is the maximum
amount of prism convergence (dioptres, noted on the prism as one would note diopters on
eye glasses) that the seated participant can accommodate at 3m and at 30cm.
5. Binocular fusion with divergence: (diopters, prism convergence units) This is the same
test as (4), except that the prisms diverge the light and the participant has to
converge (instead of diverge) their eyes to maintain focus. The score for these tests is
the maximum amount of prism divergence (diopters, noted on the prism, as one would note
diopters on eye glasses) that the seated participant can accommodate at 3m and at 30 cm.
6. Saccadic movements or oculomotor capacity: (Score = bad, medium, good) Saccadic
movements are rapid movements of the eyes that abruptly alter the point of fixation.
During this test, lights will appear and disappear - in different locations on the
screen - at a rate of 100 flashes per minute, for a total of 2 minutes. The participant
assumes a tandem stance (dominant foot placed in front of non-dominant foot and in line)
and stands an arm's length away from the screen. The participant is told to keep his/her
head still, only moving his/her eyes to focus on the appearing lights. The test result
is scored by the clinician based on a global qualitative impression over the entire 2
minute duration of the tests, with 3 separate sub-scores on an ordinal scale for quality
- for synchronization (bad, medium, good) and saccadic correction (many corrections, few
corrections, no corrections). The three sub-scores are combined into an overall score
according to our industry partner's (Apexk) proprietary algorithm.
7. Anatomic oculomotor deviation: (diopters, prism convergence units) This test measures
the natural deviation of the eyes (heterophobia) and also allows for the detection of
strabismus. In strabismus, anatomic deviation is easily detected as the individual's
eyes are misaligned, such that the individual's dominant eye is looking at the object of
interest, but the "lazy/deviated" eye is not. In heterophobia, anatomic deviation is not
visible to the naked eye; in fact, the deviation must be triggered by covering one eye
at a time in sequence, to trigger the deviation. This measure is comprised of two
identical tests, differing by distance: one occurs with an object placed 3m from the
seated participant (far vision), and the other with an object placed 30cm from the
seated participant (near vision). In this test, seated participants focus on an object.
The clinician covers and uncovers the participant's eyes to trigger movements and uses a
prism to cancel these movements. The prism that achieves this cancellation of movements
is the measure of anatomic deviation. The score of the test is the rating of the prism
that achieves the movement cancellation, for the object placed at 30cm and at 3m.
Participants with strabismus are excluded from our study as strabismus is a
contraindication to post-concussion visual training.
The main objective of this study is to evaluate the correlation between the change in
symptoms and the change in the results of the binocular vision tests. There are at least
three milestone timepoints for each participant: baseline (M1), significant improvement in
symptoms (M2), and when the participant is asymptomatic with activity or 3 months post
baseline testing (M3). Participants that do not have significant improvement at least 2 weeks
post-M1 - will be measured at 2 weeks (M*) to determine if the visual tests of function have
improved. These participants will also still be measured at M2 and M3 - for a total of 4
visits.
These milestones represent patient states: symptomatic, improved, resolution/end of study.
For our primary analyses, any patient who does not improve significantly over 3 months would
have measures at M1, M*, and M3 (end of study). Because they would not have improved in
symptoms, including them in a correlation between changes in symptoms and changes in test
results is not meaningful. Therefore, they will be excluded from the primary analyses and
will be analyzed separately. This is because the investigators are still interested in
knowing whether the test results can change in the absence of a change in symptoms. The first
step is to assess if there is a correlation between the score on BVT and the participants'
symptoms (Sx) at each time a milestone occurs. For clarity, the analysis is conducted from a
dataset where each line of data is represented by: Participant, Time (M1, M2, M3), Symptom
Score, and BVT Score. The overall statistical model is:
E [BVT] = β0 + β1*Sx + β2*M2 + β3*Sx*M2 + β4*M3 + β5*Sx*M3 + ε
Where M2=1 when the Sx and BVT are measured at M2 and is equal to 0 otherwise, M3=1 when the
Sx and BVT are measured at M3 and is equal to 0 otherwise, and ε refers to a random effect
variable that is used to account for repeated measures on the same participants. In this
model, the coefficient β1 is the association between all of the participants' symptom scores
and the BVTs. This is because M2=M3=0, so the terms to the right of β1*Sx all equal 0. In
this model, testing if the time of measurement (i.e. M1, M2, or M3) affects the correlation
is straightforward. If the correlation is the same at M2 as it is at M1, then the
coefficient, β3, will be 0. Similarly, if the correlation is the same at M3 as it is at M1,
then the coefficient, β5, will be 0. If both β3, and β5 are found to be close to zero, then
the associations are independent of the milestone at which the data were collected and the
analysis will be re-run with all the data together in a simplified analysis to increase the
power of subgroup analyses.
Next, the association in change of BVT with change in Sx will be measured. For these
analyses, the data to the relevant milestones will be restricted. The statistical models are:
E [BVT M2 - BVT M1 | M2=1, M1=1] = β0 + β6*(SxM2-SxM1) + ε E [BVT M3 - BVT M2 | M3=1, M2=1] =
β0 + β7*(SxM3-SxM2) + ε where BVT M# refers to the BVT measured at milestone number = #, and
SxM# refers to the symptom score measured at milestone number = #.
If the values of β6 and β7 are found to be similar, then the associations are, again,
independent of the milestones at which the data were collected. As above, the analysis will
be re-run with all the data together in a simplified analysis to increase the power of
subgroup analyses.
The above equations can be used to assess the association in change of total symptom score to
change in total BVT score, change in any one symptom score and change in any one BVT, and
changes in subgroups of symptom scores and changes in subgroups of BVTs. Because a deficiency
in a particular visual function would be expected to cause only certain symptoms and only
affect certain BVTs, our primary analyses will be restricted to 5 comparisons, discussed in
the outcome measure section.
Gross stereoscopic acuity and anatomic oculomotor deviation are tests that measure visual
function that existed prior to the concussion, and are, therefore, not expected to correlate
with any changes in symptoms. These tests are conducted as part of a general visual
examination.
The following symptoms in the SCAT3 are not expected to correlate with any visual tests:
pressure in the head, neck pain, sensitivity to noise, feeling slowed down, confusion,
drowsiness, trouble falling asleep, more emotional, irritability, sadness, nervous or
anxious.
The secondary analyses will include associations between the total symptom score and the
total BVT score, and the associations between the scores for each symptom and the scores for
each binocular vision measure separately. In addition, the investigators will explore
associations within subgroups of the participants based on clinician impression if there are
abnormalities in the visual system at the first visit (y/n), time between concussion and
baseline testing (<14 days, 14-28 days, >28 days), past history of concussion (y/n), and past
treatment for psychological condition (y/n).
As concussions are common, this study has the potential to contribute to improved management
for the many patients suffering from dizziness and other symptoms following a concussion.
