An interventional study of Supervised physical exercise training in Chronic Low Back Pain (CLBP), sponsored by McGill University. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-18.
Sponsored by McGill University · Not applicable, Interventional, and Treatment
This study is registered retrospectively for transparency. This mechanistic randomized controlled trial examined whether a 14-week supervised physical exercise training program reduces chronic low back pain (CLBP) by modulating frontostriatal brain connectivity and immune-related gene expression. Fifty-seven adults with CLBP were randomized to exercise training or wait-list control. Participants underwent pre- and post-intervention MRI, questionnaires, and blood sampling. The study tested whether reductions in nucleus accumbens-medial prefrontal cortex connectivity and changes in inflammatory gene expression mediated exercise-induced pain relief.
Chronic low back pain (CLBP) is associated with altered functional connectivity between the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), as well as systemic low-grade inflammation.
This mechanistic randomized controlled trial evaluated the effects of a 14-week supervised physical exercise (PE) training program on pain intensity, functional disability, brain connectivity, and peripheral gene expression in individuals with CLBP.
Participants were randomized to either:
Exercise sessions combined aerobic and resistance training. Exercise intensity was individually calibrated based on VO2max and 1 repetition maximum (1RM) assessments.
Assessments conducted pre- and post-intervention included:
The primary mechanistic hypothesis tested whether changes in NAc-mPFC connectivity and immune-related gene expression mediated exercise-induced reductions in chronic pain. Therefore, primary outcomes focused on indices of target engagement (including immune gene expression and brain connectivity) rather than clinical efficacy alone.
Note: This study was not registered prior to participant enrolment. The project was investigator-initiated and conceived as a mechanistic investigation prior to widespread mandatory registration requirements. Study recruitment and progress were also substantially influenced by the COVID-19 pandemic and associated lockdowns.
The clinical efficacy of PE for CLBP is already well established. Consequently, the primary aim of the present study was to examine the biological mechanisms through which PE may influence pain. Registration is therefore being completed retrospectively to ensure transparency.
2,930 studies on the registry are indexed under Chronic Pain; 701 are open to participants now.
This study's enrollment of 57 is close to the median of 60 across 2,161 interventional studies indexed under Chronic Pain.
Browse Chronic Pain studies →McGill University is the lead sponsor of 244 studies on the registry; 49 are open to participants now.
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Exclusion Criteria:
Physical exercise training
Behavioral: Supervised physical exercise training
Participants underwent all assessments but did not receive exercise training during the 14-week study period.
60-minute sessions 3 times weekly Aerobic + resistance training Individually calibrated intensity (VO2max, 1RM) Total duration: 14 weeks
Chronic Low Back Pain Intensity
Self-reported average low back pain intensity measured using an 11-point Numerical Rating Scale (NRS; 0-10), where 0 = "no pain" and 10 = "worst imaginable pain."
Time frame: Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 14)
Oswestry Low Back Pain Disability Index (ODI)
Pain-related disability measured using the Oswestry Low Back Pain Disability Questionnaire (10 items). Each item is scored from 0-5, yielding a total score ranging from 0-50, with higher scores indicating greater disability.
Time frame: Assessed at Baseline (Week 0) and Post-intervention (Week 14)
Nucleus Accumbens-Medial Prefrontal Cortex Functional Connectivity
Functional connectivity assessed using resting-state functional magnetic resonance imaging (rsfMRI). Seed-to-voxel analyses were performed using anatomically defined bilateral nucleus accumbens and medial prefrontal cortex regions.
Time frame: MRI acquired at Baseline (Week 0) and Post-intervention (Week 14)
Whole-Brain Intrinsic Connectivity
Intrinsic connectivity analysis (voxel-wise network centrality; root mean square of all connections) performed using resting-state fMRI.
Time frame: MRI acquired at Baseline (Week 0) and Post-intervention (Week 14)
Fractional Anisotropy of NAc-mPFC White Matter Tract
Fractional Anisotropy (FA) measured using diffusion-weighted imaging (DWI) probabilistic tractography along the white matter tract connecting the nucleus accumbens and medial prefrontal cortex.
Time frame: MRI acquired at Baseline (Week 0) and Post-intervention (Week 14)
Peripheral Blood Gene Expression (RNA Sequencing)
Gene expression levels assessed in peripheral blood immune cells using RNA sequencing (DESeq2 analysis). Transcriptomic analyses evaluated differential gene expression and pathway enrichment.
Time frame: Blood samples collected prior to Session 7 (first calibrated-intensity session, Week 3) and prior to Session 42 (final session, Week 14)
Plasma Brain-Derived Neurotrophic Factor (BDNF)
Plasma BDNF concentrations measured using Luminex multiplex assay (Human ProcartaPlex). The purpose of this outcome is to evaluate both acute and longer-term neurotrophic responses to exercise training. Acute changes were measured before and after high-intensity training sessions; long-term changes were assessed by comparing baseline levels across sessions.
Time frame: Collected immediately before and after Session 7 (Week 3) and immediately before and after Session 42 (Week 14)
Submaximal Aerobic Power (subMAP85%)
Submaximal aerobic power assessed during a graded exercise test at 85% of estimated maximal capacity. Measured in watts (W).
Time frame: Assessed at Baseline (Week 0) and Post-intervention (Week 14)
Six-Minute Walk Distance
Functional exercise capacity measured using the 6-Minute Walk Test (6MWT). Distance walked in meters during 6 minutes was recorded.
Time frame: Assessed at Baseline (Week 0) and Post-intervention (Week 14)
Plan to share: No
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