Study Design
The proposed study is a two-arm randomized control trial with test-retest design. 30 participants will be recruited and randomized into one of two muscle therapy protocols for the lumbar spine: the ‘phasic’ group (n=15) or the ‘combined’ group (n=15) (Figure 1).
Study Setting
This trial will be conducted at the PERFORM Centre (Concordia University, Montreal, QC, Canada). The proposed trial was developed in accordance with the SPIRIT 2013 statement (see Additional file 1), and was approved by the Central Ethics Research Committee of the Quebec Minister of Health and Social Services (#CCER-20-21-07). All participants will be required to sign an informed consent form prior to beginning the study.
Participant Recruitment
Participants will be recruited by students and clinicians affiliated with the Quebec Low Back Pain Consortium, through the PERFORM Centre’s website and mailing list, over social media (Facebook, Instagram), and through word-of-mouth. Individuals affiliated with the Quebec Low Back Pain Consortium who agree to be contacted for studies will receive either a telephone call or email explaining the study aims and procedure. All prospective participants will undergo a preliminary phone screening to verify eligibility. Those who pass the phone screen will be invited to the PERFORM Centre for a neurological screen, and a trial visit with the StimaWELL 120MTRS system.
Participants
Inclusion Criteria
Participants must meet all the following criteria for inclusion:
- Chronic non-specific LBP (>3 months), defined as pain in the region between the lower ribs and gluteal folds, with or without leg pain.
- Aged between 18 to 60 years old.
- English or French speakers
- Have at least score of ‘moderate’ on the Modified Oswestry Disability Index (ODI)
- Able toundergo MRI exam
Exclusion Criteria
Participants will be excluded if they meet any of the following criteria:
- Currently undergoing or having received physical therapy treatment in the previous month
- Consistent motor control training for the low back and / or consistent weightlifting, powerlifting, bodybuilding, or strongman training in the previous 6 weeks
- History of lumbar surgery
- Presence of positive lumbosacral dermatomes or myotomes
- Presence of disease which could affect the stiffness of muscle tissue (collagen tissue disease, hemiplegia, multiple sclerosis, blood clots)
- Presence of systemic disease (cancer, metabolic syndrome)
- Presence of spinal abnormality (spinal stenosis, fracture, infection, tumor, or lumbar scoliosis greater than 10 degrees)
- BMI > 30
- Presence of cardiac arrhythmia
- Pregnant and breastfeeding women
- Individuals with epilepsy
- Individuals at risk for serious bleeding
- Individuals with pacemakers or metal implants
- Individuals with aneurysms or heart valve clips
- Individuals who have taken prescribed muscle relaxants more than once a week in the previous month
Randomization
Participants will be randomized to treatment groups (1:1) using consecutively numbered sealed opaque envelopes (e.g. computer-generated randomization sequences) created by an individual not involved in the study.
Personnel
A PhD student (who is a certified athletic therapist) will conduct the majority of in-person activities, including neurological testing, ultrasound evaluations, and intervention administration. A PERFORM Centre technician will administer the MRI exam. Participant recruitment and preliminary screening will be conducted jointly between the PhD student and a research assistant working for this study’s primary investigator.
Intervention
All research activities will take place at the PERFORM Centre, Concordia University. This center houses 8000m2 of laboratories, assessment suites, and lifestyle intervention spaces. It is equipped with the instruments needed to assess this study’s primary outcomes (MRI, Ultrasound), as well as space for conducting the intervention.
All participants will receive will receive treatment with the StimaWELL 120MTRS system (schwa-medico, Germany) (Figure 2). The StimaWELL 120MTRS system is a pre-modulated IFC (interferential current) electrotherapy device. It delivers current across up to 12 channels, and offers preset pain and muscle therapy programs. The device also heats up to 40°C.
Phasic intervention group:Participants in this groupwill receive therapy at the StimaWELL 120MTRS system’s setting for phasic muscle stimulation of the lumbar spine (3 kHz, modulation 50 Hz). Tonic muscles are postural muscles composed of a majority of type I fibers, while phasic muscle are prime movers composed of a majority of type II fibers. We are choosing the phasic setting because some research has shown an increase in stiffness in the superficial multifidus (SM) in CLBP patients9, which contain a greater proportion of type II fibers in healthy individuals. The increase in stiffness could reflect a shift towards type I fiber composition in the SM in CLBP patients. Therefore, parameters which selectively target type II fibers might help reverse this process. During the initial calibration and throughout the treatments, the current intensity will be increased so that participants feel a strong but comfortable contraction. This standard of current intensity will always be maintained, although the actual output may vary over the course of treatment.
Combined (tonic and phasic) group: Participants in this groupwill receive therapy at the StimaWELL 120MTRS system’s setting for combined stimulation (3 kHz, modulation 4 Hz and 50 Hz). We are investigating the efficacy of the combined setting since 23-46% of multifidus fibers are type II fibers.27 A treatment that targets these fibers should also leads to improvements in multifidus physiology. During the initial calibration and throughout the treatments, the current intensity will be increased until participants feel a strong but comfortable contraction. This standard of current intensity will always be maintained, although the actual output may vary over the course of treatment.
Timeline: The intervention period will last 10 weeks, with treatments occurring twice a week for both groups. There is evidence that a minimum of five weeks of training are needed to induce muscular hypertrophy.28 The treatment will last 20 minutes for the first 3 weeks, 25 minutes for the second 3 weeks, and 30 minutes for the last 4 weeks; these times are in line with norms for NMES interventions.25 Additionally, participants will come to the PERFORM Centre for two pre-intervention visits (trial visit & questionnaire completion, MRI and ultrasound evaluation), and one post-intervention visit (questionnaire completion, MRI and ultrasound evaluation) for a total of 23 visits (Table 1).
Table 1. Schedule of enrolment, interventions, and assessments
|
Enrolment
|
Baseline
|
Intervention
|
Post-Intervention
|
TIMEPOINT**
|
-t1
|
0
|
t1 – 10
|
t11
|
t12-20
|
t21
|
ENROLMENT:
|
|
|
|
|
|
|
Eligibility screen
|
X
|
|
|
|
|
|
Informed consent
|
|
X
|
|
|
|
|
Neurological screen
|
|
X
|
|
|
|
|
Trial of wave-mat
|
|
X
|
|
|
|
|
Allocation
|
|
X
|
|
|
|
|
INTERVENTIONS:
|
|
|
|
|
|
|
Phasic Group
|
|
|
X
|
X
|
X
|
|
Combined Group
|
|
|
X
|
X
|
X
|
|
ASSESSMENTS:
|
|
|
|
|
|
|
NPRS Full
|
|
X
|
|
X
|
|
X
|
NPRS Pre-Post
|
|
|
X
|
post
|
X
|
|
ODI
|
X
|
X
|
|
X
|
|
X
|
BPI
|
|
X
|
|
X
|
|
X
|
PCS
|
|
X
|
|
X
|
|
X
|
MRI
|
|
X
|
|
|
|
X
|
Ultrasound
|
|
X
|
|
|
|
X
|
Primary outcome measures
MRI assessment of multifidus muscle cross-sectional area: All participants will undergo a lumbosacral MRI evaluation using the PERFORM Centre’s 3-tesla GE machine in order to assess multifidus muscle CSA and fat infiltration. MR imaging will be collected using a standard phased-array body coil with 4-mm slice thickness, 180-mm2 field of view and 512x512 matrix. Quantitative multifidus muscle measurements will be obtained from axial T2-weighted images, bilaterally at the L4-L5 and L5-S1 spinal levels, which are the most relevant levels for spinal pathologies. The multifidus muscle CSA will be measured manually at both levels on multiple slices to calculate the summative 3D volume; cross-sectional area measurements have been widely used to assess muscle size and this technique is very reliable (ICCs:0.97-0.99).29
MRI assessment of multifidus muscle fat infiltration: Following the measurement of multifidus CSA, functional CSA (e.g. the area of lean muscle tissue excluding fat infiltration) will be assessed using a highly reliable thresholding technique which differentiates lean muscle tissue from fat.30 Additionally, DIXON axial water and fat images will be used to asses percent-fat signal fraction at each spinal level according to the following equation: %FSF=(Signalfat/[Signalwater+SignalFat]x100).31
Secondary outcome measures
Ultrasound assessment of multifidus muscle %thickness change during contraction: The PERFORM Centre’s Aixplorer ultrasound unit (Supersonic Imagine, Aix-en-Provence, France) will be used to assess multifidus muscle contraction and stiffness. First, participants will be placed in a prone position, on a therapy table, with a pillow placed under their abdomen to minimize lumbar lordosis (e.g. maximum of 10° measured with an inclinometer) and instructed to relax the paraspinal musculature. The spinous process of L5 will be palpated and marked on the skin with a pen prior to imaging. Acoustic coupling gel will be applied to the skin and the ultrasound transducer placed longitudinally along the midline of the lumbar spine to confirm the location of the L5 level. The multifidus muscle will be imaged bilaterally, in the parasagittal section, allowing for the visualization of the L5/S1 zygapophyseal joints. Multifidus muscle contraction, expressed as the % thickness change from a rested to contracted position will be assessed via contralateral arm lifts while holding a small handheld weight (e.g. 1.5 to 3 pounds) based on the participant’s body weight. Participants will be instructed to raise the loaded arm 5 cm off the examination table with the shoulder in 120° of abduction and elbow 90° of flexion, following a deep inhalation and exhalation. Images will be taken after the loaded arm has been held for 5 seconds. The handed weight is designed to load the multifidus muscle to approximately 30% of maximal voluntary isometric contraction. Measurements will be obtained at L4-L5 and L5-S1 and repeated 3 times, both at rest and during contraction on each side. The average of 3 thickness ratios ([thickness contracted – thickness rest / thickness rest] x 100) will be calculated in used in the analysis. This technique is valid and reliable.32,33
Ultrasound assessment of multifidus muscle stiffness:The same position and procedure will be used to assess multifidus muscle stiffness with shear-wave elastography. This technique is based on a compressive wave that propagates within the tissue, allowing for the calculation of tissue shear wave modulus while rendering a quantitative color-coded map of tissue elasticity. Participants will be lying prone on the therapy table for 5 minutes before the lumbar multifidus is imaged at rest and during sub-maximal contractions while performing the same task as described above. Three repetitions will be performed on each side (both at L4-L5 and L5-S1) and the average shear wave modulus will be used for analysis. Finally, multifidus muscle stiffness will also be examined in a standing position, when the muscle is naturally contracting in a stabilizing role. Participants will be asked to stand barefoot on the floor with their arms relaxed on each side. In order to achieve a habitual standing posture, they were instructed to march on a spot for a few seconds and remain on the position where their feet landed. Resting shear wave modulus measurements will be acquired as described above and obtained in the standing fundamental position (e.g. arms resting naturally on each side of the body). Again, three measurements will be obtained on each side (both at L4-L5 and L5-S1) and the average shear wave modulus will be used in the analysis. This technique is valid and reliable.34,35
Pain intensity: Pain intensity will be measured with the Numerical Pain Rating Scale (NPRS). The NPRS measures pain intensity on a scale of 0 - 10, with 0 indicated no pain, and 10 indicating the worst pain imaginable. Changes of 2 or more points are clinically significant.36 At baseline, midpoint, and endpoint, participants will be asked to rate the following using the NPRS: current low back pain, current leg pain, best and worst pain low back pain over the previous week, pain sitting and with movement over the past 24 hours. Additionally, participants will be asked to rate their current low back pain prior to, and at the end of each treatment.
Pain interference: Pain interference will be measured using the Brief Pain Inventory, interference subsection (BPI). The BPI-I is a 7-item questionnaire that measures how pain interferes with activities of daily living. Each item is rated from 0-10. Higher scores indicative greater interference.
Disability: Disability will be assessed using the Oswestry Disability Index (ODI, is used to measure disability in relation to LBP. It is a 10-item scale in which each item is rated from 0-5. Higher scores indicate greater disability, and changes of >10% are clinically significant.37
All three questionnaires are valid and reliable measures of low back pain and function.36-38
Possible effect modifiers
Catastrophizing: Pain catastrophizing will be assess using the Pain Catastrophizing Scale (PCS). The PCS is a 13-item questionnaire that assesses the participant's level of catastrophizing. Each item is rated from 0-4 for a possible total of 52. Higher scores indicate greater catastrophizing, with scores above 30 being clinically significant.39
Participants will complete the BPI, ODI, and PCS at baseline, midpoint (6-weeks), and post-intervention (11-weeks).
Procedure
Trial visit: Participants who pass the phone screening will be invited for a trial visit. Upon arrival, the PhD student will ask them to sign a consent form. Second, the PhD student will assess lumbosacral dermatomes and myotomes to ensure the absence of nerve root compression. Third, participants will fill out a sociodemographic questionnaire, as well as questionnaires regarding secondary outcomes (see above). Fourth, participants will receive a 10-minute trial treatment with the StimaWELL 120MTRS system at its setting for ‘combined’ lumbar muscle therapy.
Wave-mat calibration: The StimaWELL 120MTRS system delivers current at a given intensity across up to 12 channels. However, in the presence of pain or injury the current may not be felt equally across channels. Therefore, prior to the trial, the wave-mat will be calibrated to ensure that the current is equally felt across all channels. A paper towel will be sprayed with warm water and laid over top of the wave-mat. Participants will be asked remove their top (and unbuckle their bra, if applicable), lie supine on the towel with knees bent, and lower the top of their underwear so that their coccyx is touching the lowest channel. A blanket will be provided for privacy. During the initial phase of calibration, the current travels the length of the wave-mat, from bottom to top, in repetitive fashion. The current will be increased to tolerance (i.e. until participants feel a strong, but non-painful, sensation). Then, the current will be adjusted, channel by channel (from bottom to top), to ensure that each channel is set to the appropriate intensity. Once this is complete, the current will be adjusted from side-to-side, in groups of two channels (from bottom to top), to ensure the intensity is the same from one side to another at a given level. This completes the calibration. This process will be repeated prior to the start of participants’ 5th, 9th, 13th, and 17th treatments, to account for unilateral and segmental adaptations, and to ensure the multifidus is appropriately stimulated.
Data Monitoring
Adverse events: The occurrence of adverse events in response to the treatment (ex: muscle soreness, temporary increase in pain or stiffness) will be monitored by the PhD student during the intervention using open-ended questions.
Co-interventions: Participants will be asked about co-interventions (physiotherapy visits, medication, exercise, injection) during each visit. Any co-interventions will be recorded.
Treatment modification: During all sessions, participants will be provided a remote to increase or decrease the intensity of the current to tolerance, as needed.
Sample size calculation
The effect of NMES on multifidus muscle morphology and function has never been thoroughly investigated in subjects with CLBP. Therefore, we did not conduct a power analysis and will recruit a sample of 30 subjects with CLBP (15 in each group). This study will serve as a pilot RCT, to investigate the feasibility and effectiveness of using NMES in this specific population before conducting a larger RCT.
Statistical Analysis
We will perform an exploratory data analysis on participants’ sociodemographic characteristics and to verify normality assumptions. Paired t-tests or Wilcoxon sign-rank tests will be used assess within-group changes, pre-to-post intervention, for all primary outcome measures. Independent t-tests or Mann Whitney-U tests will be used to assess between-group changes, pre-to-post intervention, for all primary outcome measures. We will use either a two-way repeated measures ANOVA or Kruskall-Wallis tests to determine changes over time for secondary outcome measures. For all tests, statistical significance will be set at p < 0.05.