Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03151200 |
| Other study ID # |
B2014:117 (HS18266) |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 30, 2014 |
| Est. completion date |
December 2020 |
Study information
| Verified date |
October 2018 |
| Source |
University of Manitoba |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to assess the effectiveness of combining binocular treatment
with repetitive transcranial magnetic stimulation (rTMS) in improving the vision of adults
with amblyopia. This study also seeks to assess the effect of this combined treatment on
cortical neural function and functional connectivity.
Description:
Prior to the study, ocular misalignment and refraction abnormalities will be corrected This
correction is part of standard patient care rather than a procedural component of the current
study.
Procedure Participants will undergo one hour structural and functional MRI prior to their
treatment. We will perform an interim analysis of the fMRI results once five amblyopic
patients have completed the fMRI study. If the data shows significant differences in the
resting state visual network in amblyopia patients compared to the existing normal visual
resting state, we will pursue the fMRI study with the remaining 15 participants. Misalignment
of the eyes will be corrected prior to a patients' participation by using prisms (if
medically indicated). This correction is part of standard patient care rather than a
procedural component of the current study. Participants will be randomly appointed to
initially be in either the sham or the treatment group (10 patients in each group). All
patients will receive five days of one hour visual binocular training by playing a specially
designed falling blocks videogame on a computer screen that will be individually calibrated
for each person. Group one will receive 18 minutes of rTMS at the beginning of their visual
training every day for 5 days. Group two will receive 18 minutes of TMS followed by sham
visual training every day for 5 days. At the end of five days, participants will switch
groups. Participants will be blind as to whether they receive sham or real binocular
treatment on each occasion.
A sensorimotor visual profile, including visual acuity, suppression, stereovision,
binocularity, contrast sensitivity and eye alignment, will be completed for each patient at
baseline, after five sessions, and at the end of the treatment. This profile will be
completed using the PVVAT system, Worth-4-Dot test, Randot stereovision test, anaglyphic
dichoptic coherence motion threshold with red-green glasses (using Psykinematix vision
system), cross cover test with prism bars. fMRI will be repeated post-treatment only for
individuals who showed abnormal fMRI at baseline. This second scan will investigate whether
the treatment affected and normalized the resting state visual network.
Functional MRI:
All scanning will be performed on a 3.0 T Siemens Tim Trio scanner equipped with a 12-channel
head coil. Scanning will take place on up to three visits: Pre-treatment (retinotopic
mapping), and two post treatment scans.
Pre-treatment: structural, resting state and BOLD functional MRI (fMRI) data will be
acquired. Participants will complete a structural MRI scan at the beginning of each MRI
session. This is a high-resolution 3-dimensional image of the whole brain (Imaging
parameters: MPRAGE, 1mm thick slices, zero spacing between slices, TR = 1900 ms, TE = 2.2 ms,
in plane resolution of 0.94 x 0.94, 256 x 256 matrix size with a 24 cm field of view, 176
volumes, resulting in a 8 minute 6 second scan time.
After the high-resolution image has been acquired, the resting state functional MRI data will
be acquired with the following parameters: Siemens echo planar imaging (EPI) sequence, 3 mm
thick slices, zero spacing between slices, repetition time of 3000 ms, echo time of 30 ms,
flip angle of 90°, 64 x 64 matrix size, 24 cm field of view, 140 volumes, resulting in a 7
minute 9 second scan time. During this session the patients will close their eyes and rest.
Following the resting state fMRI session we will perform task-based and retinotopic mapping
using standard wedge and ring protocols to evoke blood oxygen level-depended (BOLD) response
in the visual cortex. (Li X, Dumoulin SO, Mansouri B, Hess RF. The fidelity of the cortical
retinotopic map in human amblyopia. Eur J Neurosci. 2007;25:1265-1277.29). Functional data
will be acquired using a T2-weighted gradient echo EPI sequence (retinotopic mapping, TR =
1200 ms, TE = 30 ms, flip angle = 65°, voxel resolution 2.5 x 2.5 x 2.5 mm; post treatment
scans, TR = 2000 ms, TE = 30 ms, flip angle = 90°, voxel resolution = 3.0 x 3.0 x 3.0 mm).
Stimuli will be presented monocularly and each eye will be mapped separately. Borders of
retinotopic areas and corresponding regions of interest will be defined using an averaged map
of the left and right eye in each participant. During fMRI, participants will be presented
with visual stimuli (viewed over an MRI compatible white screen through a coil-mounted
mirror) and perform a reaction time task where they will simply press a button when they
detect a change in the fixation point. The task will be unrelated to the stimuli used.
The subsequent fMRI scanning sessions will be performed after two week of Transcranial
Magnetic stimulation (TMS) and binocular treatment, which will assess the effect of rTMS plus
sham/real binocular treatment on the response of the visual cortex to inputs from the
amblyopic versus fellow fixing eye. We will use the localizing information from the first
session. The resting state and task-based fMRI will be repeated.
1. Pre -treatment visit:
a. Localizer to find slice plan (1-2 min) b. MPRAGE anatomical (7-10 min) c. Resting state -
eyes closed stay awake (7-10 min) d. Retinotopic mapping (48 min PLUS time to alternate eye
patch between runs) i. 4 scans of block design amblyopic eye covered
1. 2 eccentricity,
2. 2 polar angle,
3. 2 clockwise,
4. 2 counterclockwise, ii. 4 scans of block design fellow fixing eye covered
One week of either Group A) rTMS and true binocular treatment or Group B) rTMS and sham
binocular treatment 2. Post treatment visit:
1. Localizer (1-2 min)
2. MPRAGE anatomical (7-10 min)
3. Resting state - eyes closed stay awake (
4. not retinotopic mapping
5. fMRI block design
i. checkerboard stimulus 4 scans per session per eye One week of CROSS OVER treatment Group
A) rTMS and sham binocular treatment or Group B) rTMS and binocular treatment fMRI analysis
Resting state fMRI data will be pre-processed to reduce artifacts and noise-related signal
components. Following pre-processing, data will be analyzed at the individual level using
Independent Component Analysis. The individually analyzed data will then be standardized to
stereotactic space using a Talairach atlas. The standardized data will be run through a
Self-Organized Grouped ICA which will summarize the ICA data from all participants. An
analysis of variance will be used to assess differences in functional connectivity in brain
regions between the groups (pre- and post-rTMS treatment).
Potential harms and benefits It is our hope that as a result of their participation in this
study, patients will see an improvement in many aspects of their vision, including overall
visual acuity and contrast sensitivity.
There is a chance that improving vision in the weak eye may result in double vision if the
position of the eyes (alignment) is suboptimal. This double vision may spontaneously subside
over time as the training effect wears off (in the absence of further training). If double
vision persists, participants may have to be referred to neurology, optometry or
ophthalmology clinics for symptom management. Patching over the weak eye may be required in
order to eliminate the double vision, decreasing vision in the weak eye in an effort to
returning vision to what it was before participation in the study. Other treatments for
double vision include optical correction with glasses that contain prisms or surgical
intervention to align the two eyes. The latter methods help fuse images from the two eyes in
most of cases.
The rTMS procedures proposed for this study are well within recommended safety guidelines, so
the risk of adverse events is slim. TMS can cause twitching of the scalp or face muscles
during stimulation, which may be uncomfortable. About 1 out of 10 subjects report a headache
after the TMS measurement, which is usually mild and transient. If needed, the headache can
be treated with mild over-the-counter pain medicine, such as acetaminophen/Tylenol. The risk
of seizure from rTMS is elevated in individuals with a history of epilepsy or a family
history of seizures, which is why these conditions are exclusion criteria for this study.
