Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03829644 |
| Other study ID # |
Pro00086518 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 20, 2019 |
| Est. completion date |
February 20, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Despite the high prevalence of low back pain, little is still known about its underlying
pathology. Only a small proportion of people (~1%) have a diagnosable pathoanatomical entity
causing low back pain. The other types of back pain are classified as non-specific low back
pain. Thus, current back pain management typically focuses on relieving symptoms. This is
largely ineffective without understanding the cause. Yet, there are some pathologies which
are thought to be associated with low back pain.
Vertebral bone marrow oedemas are now known to be a hallmark feature for low back pain. There
are three types of vertebral bone marrow oedemas. Type I oedemas are dynamic lesions that may
progress to a higher grade, stop, or even return to normal. Although the precise cause of
type I oedemas is not well understood, loading on the spine plays a key role in its
development. Lumbar braces are known to reduce loads on the spine. Thus, they may reduce the
size of oedema by modifying loads on the spine. The investigators already know that wearing a
lumbar brace reduces pain in people with back pain and type I vertebral bone marrow oedemas.
Unfortunately, there is no study showing that pain reduction with bracing is associated with
a reduction of oedema. The goal of this study is to determine if wearing a lumbar brace for
six weeks will reduce the dimensions of type I vertebral bone marrow oedema.
Description:
Purpose
Modic changes are now known to have a high specificity for low back pain. Modic changes
represent bone oedema and are dynamic lesions that may progress to a higher grade, stop, or
even reverse to a lower grade. Although the precise aetiology of Modic changes is not well
understood currently, abnormal mechanical loading plays a key role in their development and
progression. Biomechanical studies have demonstrated that abnormal shear forces acting on the
vertebral endplate could lead to endplate microtrauma and marrow oedema correlating with type
I Modic changes. This suggests that Modic changes may be ideal structural targets for
treatment designed to alter vertebral loading. The main goal of this project is, therefore,
to mitigate, stop, or reverse Modic lesion progression and their associated pain through the
use of lumbar orthoses that can modify loads acting on the lumbar spine by limiting both fine
and gross trunk movements, and thus decreasing demands for muscular activities. As this
effect of bracing likely reduces biomechanical stress on the vertebral endplate as well,
lumbar orthoses should, in theory, be able to impact bone marrow lesions by normalizing
lumbar loading.
Hypothesis
I) Modification of the mechanical load in the lumbar spine using a semi-rigid lumbosacral
orthosis for six weeks will reduce the dimensions of Modic changes
II) The same bracing protocol will help mitigate, stop, or reverse the progression of Modic
changes;
III) These morphologic changes will be associated secondarily with a reduction in pain and
discomfort and an increase in spinal function.
Although the precise aetiology of Modic changes is not well understood, abnormal mechanical
loading likely plays an important role in their development and progression. Biomechanical
studies have demonstrated that abnormal shear forces acting on the vertebral endplate could
lead to endplate microtrauma and marrow oedema correlating with type I Modic changes. Modic
changes are dynamic lesions that may progress to a higher grade, stop, or even reverse to a
lower grade. All of this suggests that Modic changes may be ideal structural targets for
treatment that can alter vertebral loading.
Objectives
I) PRIMARY: To determine if wearing a semi-rigid lumbosacral orthosis for six weeks will
significantly reduce the dimensions of Modic changes;
II) SECONDARY: To determine if this same bracing protocol will induce morphological and
textural changes in the vertebra;
III) SECONDARY: To determine if these changes are associated with improvements in pain and
function;
IV) EXPLORATORY: To determine if this same bracing protocol will reduce prescription and/or
consumption of analgesics;
V) EXPLORATORY: To determine if this same bracing protocol will reduce the low back pain
related use of health resources.
Methods/Procedures
This project is a prospective, superiority, 1:1 parallel randomised control trial with
concealed allocation. Randomisation arms include semi-rigid lumbar bracing and no bracing.
Superiority will be based on a minimally clinically significant difference of the Modic
changes (our primary outcome measure).
After obtaining approval from the University of Alberta's Health Research Ethics Board, the
investigators will invite 46 volunteers with benign low back pain and MRI evidence of type I
Modic changes to consent and participate in this study. the investigators will recruit
volunteers from the University of Alberta Hospital who have obtained clinical MRIs in their
regular course of care who have been identified as having a Modic change in their lumbar
spine.
A co-investigator will review all routine lumbar spine MR images from the Department of
Radiology of the University of Alberta to identify possible participants who have been
identified as having a Modic change as part of their usual clinical care (a waiver for
consent will be requested in this application). A letter of invitation will then be sent to
those persons inviting them to contact us for more information about the study. A research
assistant will respond to all inquiries and then administer the Numeric Pain Rating Scale and
the Oswestry Disability Index to further screen the participants for minimal score values to
prevent floor effects of outcome response. If potential participants meet these inclusion
criteria and provide written informed consent, the research coordinator will enrol them in
the study.
After enrolment, each participant will be given a study number to maintain and track her/his
records. The participant will be then provided with a Research Electronic Data Capture
(REDCap) secure web address to complete various data collection surveys (e.g. demographics).
All participants will be instructed that the current study will not substitute their current
back pain management program. Participants in the intervention arm will be fitted with a
semi-rigid prefabricated lumbar brace (Horizon 627 Lumbar Brace, Aspen Medical Company, Oak
Canyon, Irvine, CA 92618). The brace is a one-size adjustable design to fit waists ranging
from 24-70 inches. Participants will be instructed to wear the brace for six weeks. As this
brace is semi-rigid, it does not prevent motion - only reduces motion in the lumbar areas.
Our prior work and that of others have shown that this type of bracing does not reduce spinal
function and is not associated with atrophy.
Baseline session
The investigators will collect demographics (e.g., age, sex, family physician contact),
previous history/comorbidities, past imaging, and current treatment. As the initial MR images
used to identify potential participants may be taken for proposes other than visualizing
Modic changes, their quality may not be appropriate for quantitative image processing.
Therefore, all participants will undergo baseline MR imaging. Imaging protocols for the
sagittal T2-weighted scans will be as follows: position: supine; repetition time: 1960 ms;
echo time: 106 ms, slice thickness:4.0 mm; and matrix size:512×512. Likewise, the anticipated
MRI parameters for the fast spin-echo sagittal T1-weighted scans will be as follows:
position: supine; repetition time: 340 ms; echo time: 12.9 ms; slice thickness: 4.0 mm and
matrix:512×512. The sequences and timings will be kept consistent across all participants.
The investigators will randomise participants to one of two arms: semi-rigid lumbosacral
orthosis or no brace following imaging to confirm the presence of Modic changes in these new
images.
Randomisation
The investigators will deploy the REDCap randomisation tool to assign participants evenly
into the intervention and control groups. The tool uses a defined parameter (subject ID in
this study) to create a template allocation table. The on-site research assistant will enter
each participant's REDCap record and then click the "Randomize" button. This will trigger
REDCap to check the allocation table and display the group to which the participant should be
assigned. The assignment is permanent and not editable within the participant record and,
like all other activity within REDCap, is tracked and not modifiable in the audit log.
MR imaging
After enrollment, all subsequent imaging will be carried out at the MRI Research Center at
Edmonton's Cross Cancer Institute using a 3T whole-body Philips MRI scanner (Philips
Healthcare Intera). Based on a previous study, the anticipated MRI parameters for the
sagittal T2-weighted scans will be as follows: position: supine; repetition time: 1960 ms;
echo time: 106 ms, slice thickness:4.0 mm; and matrix size:512×512. Likewise, the anticipated
MRI parameters for the fast spin-echo sagittal T1-weighted scans will be as follows:
position: supine; repetition time: 340 ms; echo time: 12.9 ms; slice thickness: 4.0 mm and
matrix:512×512. The sequences and timings will be kept consistent across all participants.
Self-reported questionnaires
The investigators will measure participants' pain level using the Numeric Pain Rating Scale.
The investigators will use the Roland-Morris Disability Questionnaire and the Oswestry
Disability Index to measure participant function and disability level.
Immediately after wearing the brace (only the intervention group)
To assess the immediate impact of the brace, participants will use self-reported outcome
tools on the REDCap to quantify pain (Numeric Pain Rating Scale) immediately after wearing
the brace.
To measure the quality (how tightly the brace has been worn) and quantity (how much time the
brace has been worn) of brace usage, a low-powered portable heat and load monitoring system
will be embedded within the pressure pad of the brace. The force measurement part of the
monitoring system is sensitive to the forces normal to the brace surface, but not to shear
forces, and can be deployed to monitor the quality of the brace wear by participants.28 The
temperature part of the monitoring system gives an accurate and stable output over the
temperature range from 5 °C to 50 °C,29 and can be deployed to monitor how long the brace has
been worn during the brace treatment.
Weeks 1 to 6 follow-ups
All participants will receive a series of text questions by mobile phone 3 times a week for 6
weeks. The questions will collect data related to the pain (Numeric Pain Rating Scale),
spinal function (Roland-Morris Disability Questionnaire and Oswestry Disability Index), brace
usage, and analgesic consumption.
Week 6 MRI scanning
At this visit, the investigators will administer the Numeric Pain Rating Scale, Oswestry
Disability Index, and self-reported Roland-Morris Disability Questionnaire. All participants
will then undergo a follow-up MRI scan using the very MR imaging protocol.
The costs of the first and second MRI will be paid by a grant from the Alberta Spine
Foundation. The investigators will not use the clinical images taken at the designated
centres in this study. These initial clinical images are only used for Dr. Dhillon to
identify potential participants. The investigators will not use them further in our study as
their specific parameters vary too much to be used in our study.
Week 7 to 52 follow-ups
The investigators will continue to collect a series of outcomes and interview questions
(Numeric Pain Rating Scale, Roland-Morris Disability Questionnaire, Oswestry Disability
Index, brace usage, and analgesic consumption), by short message service at 4, 8 and 12
months.
End of the enrollment
The investigators will use participant personal health numbers (obtained at baseline with
consent) to perform an exploratory analysis through the Alberta Bone and Joint Health Network
of health care resource utilization in the year before and during the trial (e.g.
prescriptions filled, primary care and emergency department visits, imaging usage, etc.).
Image and Data Analysis
Blinding
Due to the nature of each intervention, blinding will not be feasible for participants.
However, the MR technician, outcomes assessor, outcome adjudicators, and the statistician
will be blinded to the actual allocation. The actual allocation will not be disclosed to the
research assistant responsible for image processing, data entry, and the statistician. The
investigators will develop two interpretations of our results based on a blinded review of
the primary outcome data (intervention A vs. intervention B). One scenario will assume
intervention A was brace and the other will assume intervention A was routine
recommendations. Only after our team has agreed that there will be no further changes in the
interpretation of the scenarios will the randomisation code be broken, and the correct
interpretation used in manuscript preparation.
Image analysis and processing
Image processing will be carried out offline using highly reliable Matlab®-based (MathWorks,
Natick, MA) lumbar spine analysis software for MRI images developed by our team. The software
uses signal and textural variations in the neighbouring structures to semi-automatically
segment vertebrae and intervertebral discs from adjacent tissues. It then calculates
traditional measures such as mean signal intensity, area, disc height, width, the range of
signal intensity as well as more than two hundred textural features, including kurtosis,
skewness, contrast, homogeneity, energy, and correlation for each region of interest.
Statistical Analysis
The investigators will employ a repeated measure ANOVA to compare pain level between groups.
The investigators will use age, gender, brace type, and pain severity as potential covariates
if randomisation does not result in group equivalence. The investigators will also estimate
the effect size of differences between and within the groups for pain using Cohen's d.
