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Completed

NCT Number: NCT07480460

Brain and Gene Expression Responses to Exercise in Chronic Back Pain

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.

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Key information

Conditions

Chronic Low Back Pain (CLBP) Back Pain Behavior Chronic Pain Inflammation Motor Activity Neurologic Manifestations Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal

Montreal, Quebec, H3W 1W4, Canada

About this study

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:

  • Supervised exercise training (3 sessions per week, 60 minutes per session, 14 weeks), or
  • Wait-list control.

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:

  • Resting-state functional MRI
  • Diffusion-weighted imaging
  • Self-reported pain and disability questionnaires
  • Cardiorespiratory and functional testing
  • Blood sampling for BDNF and RNA sequencing

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18 years
  • Chronic low back pain ≥ 3 months
  • Pain present at least half the days over the past 6 months
  • Average pain intensity ≥ 3/10 during week prior to enrollment

Exclusion criteria

  • Diabetes
  • Neurological disorder
  • Psychiatric disorder
  • Significant cardiorespiratory disease
  • Under 18 years of age

Treatment and study plan

Supervised physical exercise training

Behavioral

60-minute sessions 3 times weekly Aerobic + resistance training Individually calibrated intensity (VO2max, 1RM) Total duration: 14 weeks

Primary outcomes

  1. Chronic Low Back Pain Intensity

    Time frame: Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 14)

    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."

Secondary outcomes

  1. Oswestry Low Back Pain Disability Index (ODI)

    Time frame: Assessed at Baseline (Week 0) and Post-intervention (Week 14)

    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.

  2. Nucleus Accumbens-Medial Prefrontal Cortex Functional Connectivity

    Time frame: MRI acquired at Baseline (Week 0) and Post-intervention (Week 14)

    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.

  3. Whole-Brain Intrinsic Connectivity

    Time frame: MRI acquired at Baseline (Week 0) and Post-intervention (Week 14)

    Intrinsic connectivity analysis (voxel-wise network centrality; root mean square of all connections) performed using resting-state fMRI.

  4. Fractional Anisotropy of NAc-mPFC White Matter Tract

    Time frame: MRI acquired at Baseline (Week 0) and Post-intervention (Week 14)

    Fractional Anisotropy (FA) measured using diffusion-weighted imaging (DWI) probabilistic tractography along the white matter tract connecting the nucleus accumbens and medial prefrontal cortex.

  5. Peripheral Blood Gene Expression (RNA Sequencing)

    Time frame: Blood samples collected prior to Session 7 (first calibrated-intensity session, Week 3) and prior to Session 42 (final session, Week 14)

    Gene expression levels assessed in peripheral blood immune cells using RNA sequencing (DESeq2 analysis). Transcriptomic analyses evaluated differential gene expression and pathway enrichment.

  6. Plasma Brain-Derived Neurotrophic Factor (BDNF)

    Time frame: Collected immediately before and after Session 7 (Week 3) and immediately before and after Session 42 (Week 14)

    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.

Other outcomes

  1. Submaximal Aerobic Power (subMAP85%)

    Time frame: Assessed at Baseline (Week 0) and Post-intervention (Week 14)

    Submaximal aerobic power assessed during a graded exercise test at 85% of estimated maximal capacity. Measured in watts (W).

  2. Six-Minute Walk Distance

    Time frame: Assessed at Baseline (Week 0) and Post-intervention (Week 14)

    Functional exercise capacity measured using the 6-Minute Walk Test (6MWT). Distance walked in meters during 6 minutes was recorded.

Sponsors and collaborators

Lead sponsor

McGill University

Other

Collaborators

  • Canadian Institutes of Health Research (CIHR)

Registry information

Official study title

Frontostriatal Connectivity and Gene Expression in Exercise-induced Relief of Back Pain

Acronym: CLBPE

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Mar 18, 2026
Registry last updated
Mar 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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