Background
Methods and study design
Study participants
Inclusion criteria |
1. Between 18 and 50 years of age 2. Answer “yes” to the following questions:
▪ Have you had two or more episodes of low back pain (LBP) in the past 12 months with at least one of the episodes causing a restriction of work or leisure time activity? 3. Body mass index between 17 and 37 kg/m2
4. With no condition that could limit participation in supervised resistance training exercise based on the Physical Activity Readiness Questionnaire (PAR-Q) 5. Sedentary lifestyle as measured by a classification of “low” or “moderate” levels of physical activity based on scoring criteria of the International Physical Activity Questionnaire (IPAQ) 6. Exhibit low trunk extensor endurance defined as a time to task failure during the modified-Sorensen test of <176 seconds. |
Exclusion criteria |
1. Participate in progressive resistance exercise within the previous 24 weeks prior to screening 2. Experienced limb amputation (except for toes) and/or any fracture within 24 weeks 3. Have a personal history of the following neurological disorders: Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, or stroke 4. Have a personal history of the following cardiorespiratory disorders: congestive heart failure, myocardial infarction, or peripheral vascular disease 5. Have conditions (e.g., myasthenia gravis, myositis, muscular dystrophy or myopathy, including drug-induced myopathy) leading to muscle loss, muscle weakness, muscle cramps or myalgia 6. Have a personal history of the following musculoskeletal disorders: rheumatoid arthritis, spinal or pathological fractures, scoliosis, spondylolisthesis, avascular necrosis or osteonecrosis, severe osteoarthritis. (Including a history of spinal surgery or a hip arthroplasty). 7. Have a personal history of any of the following conditions or disorders not previously listed: diabetes, fibromyalgia, active cancer, severe obesity (i.e., body mass index greater than 35 kg/m2), clinical depression (i.e., subjects who score 24 or higher on the Center for Epidemiology Depression Scale) 8. Have chronic or relapsing/remitting gastrointestinal disorders such as inflammatory bowel diseases, irritable bowel syndrome or gastrointestinal infections within 28 days of screening 9. Have an acute viral or bacterial upper or lower respiratory infection at screening 10. Have moderate or severe chronic obstructive pulmonary disease 11. Report back pain greater than 4 (on a 10- point numerical pain rating scale) at screening 12. Have a leg length discrepancy >3 cm 13. Exhibit abnormal or uncontrolled blood pressure (BP) at the screening visit (i.e., diastolic BP >100 and/or systolic BP >160 mmHg). If taking anti-hypertensive medication, have to be on stable doses of medication for more than 3 months 14. Exhibit abnormal electrocardiogram findings indicative of left ventricular hypertrophy (based on Cornell voltage criteria) at the screening visit 15. Have a current or recent history (within 1 year of screen) of heavy alcohol consumption (men ≥21 drinks/week, 4 drinks/day; women ≥14 drinks/week, 3 drinks/day) or drug abuse 16. Have a current or previous use of any drugs known to influence muscle mass or performance within 24 weeks 17. Report being pregnant, lactating, or that they anticipate becoming pregnant in the next year 18. Report unexplained weight loss over the past month (>10 lbs) 19. Report they have pending litigation related to an episode of LBP or are receiving any type of disability services 20. Use of systemic glucocorticoids within 12 weeks prior to screening 21. Report having received any treatment for LBP by a health care practitioner in the past 6 weeks22. Have contraindications for exposure to a magnetic field |
Randomization and blinding
Study time line
Study procedure | Screen/baseline period | Intervention period | Follow-up | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Screen visit 1 | Baseline visit 2 | Visits 3–6b
| Visits 7–10b
| Visits 11–14b
| Visits 15–18b
| Visits 19–22b
| Visit 23a
| Visit 24a
| Non-visit surveys | |
Day (window, ± days) | −21 to −1 | −21 to −1 | 1 − 14 | 15 − 28 | 29 − 42 | 43 − 56 | 57 − 70 | 71 ± 4 | 154 ± 7 | Once every 4 weeksc
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Screening/baseline: | ||||||||||
Informed consent | X | |||||||||
Inclusion/exclusion | X | |||||||||
Medical history | X | |||||||||
Weight | X | X | X | |||||||
Height and demographics | X | |||||||||
PAR-Q, IPAQ | X | |||||||||
Electrocardiogram | X | |||||||||
Sorensen test | X | |||||||||
Randomization | X | |||||||||
Exercise sessions: | ||||||||||
Exercised
| X | X | Xd
| X | X | |||||
Efficacy: | ||||||||||
MRI | X | X | X | |||||||
DEXA | X | X | X | |||||||
Strength | X | X | X | |||||||
Endurance | X | X | X | |||||||
Pain and disability | X | X | X | X | X | X | X | X | X | X |
Treatment acceptability | X | X | X | X | X |
Outcome measures
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Trunk extensor muscle cross-sectional area (primary outcome): magnetic resonance imaging (MRI) will be performed with a 0.25-Tesla Musculoskeletal MRI system (Esaote G-Scan Brio, Genoa, Italy) to acquire contiguous transverse T-1 weighted spin echo image slices in the trunk region between L2 and L5, with a slice thickness of 10 mm. To ensure the consistency within/among subjects, the isocenter will be positioned at the midpoint of the L3/L4 intervertebral disc. The number of the slices will vary across participants to cover the region of our interest. Prior to all MRIs subjects will lie supine for at least 15 minutes to minimize the effects of fluid shifts on volumetric calculations. The post-testing MRI scan will be obtained 3 days after the final training session to minimize the effects of exercise-induced fluid shifts. After scanning, images will be transferred to a computer for calculation of CSA. Muscle anatomical CSA will be calculated for (1) the quadratus lumborum, (2) iliocostalis lumborum/longissimus thoracis (these two muscles will be grouped due to the difficulty in defining distinct fascial borders in some subjects), and (3) the multifidus. This calculation will be based on an average of three slices obtained from the center of the respective muscles
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Trunk extensor muscle strength (secondary outcome): participants will perform three maximum isometric TE contractions on a customized lumbar extension dynamometer (MedX; Ocala, FL, USA) at 36° from full extension (additional trials will be provided as needed if subjects continually exert more force with each trial). Each contraction will last approximately 5 seconds with at least a 60-second interval. Muscle strength will be defined as the highest value recorded in any trial. Muscle strength for leg extensors, plantar flexors, and elbow flexors will also be assessed to permit the calculation of the training intensity for the exercise programs. For all strength assessments, time-series torque signals will be collected at 500 Hz by a Biopac MP150 system (Biopac Systems Inc., Santa Barbara, CA, USA)
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Trunk extensor muscle endurance (secondary outcome): participants will perform a sustained, submaximal isometric trunk extension contraction at 20 % of their baseline muscle strength until volitional task failure on a customized lumbar extension dynamometer at 36° from full extension. During this task, the target will be displayed on a computer monitor placed in front of the participant and the time to task failure will be quantified. The time-series torque signal will be collected at 500 Hz by a Biopac MP150 system (Biopac Systems Inc., Santa Barbara, CA, USA)
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Pain and perceived disability (tertiary outcomes): a 0–10 numerical pain rating (NPR) scale will be used to quantify LBP. The Roland Morris Disability Questionnaire, which consists of 24 items related to LBP, will be used to quantify perceived disability [67]. These data will be used to calculate the rate, duration, pain intensity, and disability of LBP recurrence during the follow-up period. To analyze LBP recurrence, we will first define an episode of LBP as a period of pain in the lower back lasting for more than 24 hours, preceded and followed by a period of at least 1 month without LBP. This definition is consistent with that suggested by de Vet and colleagues [68]. We will then compute the rate of LBP recurrence as the number of episodes per quarter, duration as how long on average each episode lasted within each participant, and intensity as the mean and maximum pain/disability scores over the follow-up period as well as during an episode of LBP occurrence
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Body composition. Dual-energy X-ray absorptiometry (DEXA: Hologic Discovery QDR model Series, Waltham, MA, USA) will be performed to assess whole body and regional lean mass as well as whole body and regional fat mass. Participants will be instructed to adequately hydrate prior to the body composition assessment. These data will permit us to determine the effects of the exercise interventions on increasing appendicular lean mass and examine whether individuals with the greatest increases in appendicular lean mass exhibited the greatest “cross-transfer” of effect to the TE CSA (measured via MRI)
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Treatment acceptability. Treatment acceptability will be determined by administering the Treatment Evaluation Inventory survey at the end of every fourth exercise session [69]
Exercise interventions
Group | Blood flow restriction | Frequency | Exercise regimen |
---|---|---|---|
Exercise control group | No | Twice weekly | • 3 sets of leg extension, calf raises, and arm curls at 25 % of individuals’ isometric MVC to failure (30–60 seconds rest between sets) • 3 sets of trunk extension at 25 % for 15 repetitions (30–60 seconds rest between sets) • Up to 3 minutes rest between each exercise station |
BFR exercise group | • Pressure cuffs applied to the upper leg during legs exercises and upper arms during arm curls • Pressure is maintained throughout the 3 sets for the respective exercises | Twice weekly | • 3 sets of leg extension, calf raises, and arm curls at 25 % of individuals’ isometric MVC with BFR to failure (30–60 seconds rest between sets) • 3 sets of trunk extension at 25 % of individuals’ isometric MVC for 15 repetitions (30–60 seconds rest between sets) with BFR on upper arm • Up to 3 minutes rest between each exercise station |