Neuroimmune Responses to Exercise in Chronic Back Pain

NCT07497425 | Recruiting

• 1 other identifier: eCLBP
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this mechanistic clinical trial is to learn how physical exercise affects the body and brain in people with chronic low back pain. The study will examine whether a 12-week online exercise program changes these measures compared with a waitlist group. Researchers will also study immune activity and brain function in people with chronic low back pain and compare them with healthy participants. Participants will complete questionnaires, provide blood samples, and undergo brain imaging scans.

Conditions

Chronic Low Back Pain (CLBP)

Keywords

mechanisms; immune system; inflammation; brain; chronic pain; exercise

Outcome Measures

Primary Outcomes (1)

• Chronic Low Back Pain Intensity

  Self-reported low back pain intensity averaged over the past 7 days, measured using an 11-point Numerical Rating Scale (NRS; 0-10), where 0 = "no pain" and 10 = "worst imaginable pain." Item from the NIH minimum dataset on research standards for chronic low back pain. Data collected in REDCap.

  Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12). In addition, assessed daily through electronic pain diaries.

Secondary Outcomes (18)

• Peripheral Blood Gene Expression (RNA Sequencing)

  Blood samples collected at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12). In addition, samples also collected 14, 48 hours and 2 weeks after the first exercise session or at equivalent times for waitlist participants

• Nucleus Accumbens-Medial Prefrontal Cortex Functional Connectivity

  MRI acquired at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

• Fractional Anisotropy of NAc-mPFC White Matter Tract

  MRI acquired at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

• Whole-Brain Intrinsic Connectivity

  MRI acquired at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

• Tonic Pain Signature (ToPS)

  MRI acquired at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

Other Outcomes (10)

• Pain Catastrophizing Scale

  Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

• Tampa Scale of Kinesiophobia

  Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

• Pain Self-Efficacy Questionnaire

  Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 12)

Study Arms (3)

Active intervention

EXPERIMENTAL

Physical Exercise Training

Behavioral: Physical Exercise

Waitlist

NO INTERVENTION

Participants assigned to the waitlist group will not receive the physical exercise program during the 12-week intervention period but will continue their usual care. After completion of the study assessments, they will be offered access to the exercise program.

Healthy controls

OTHER

Sex- and age-matched healthy volunteers will only participate in the first 2 weeks of PE intervention

Behavioral: Physical Exercise

Interventions

Physical Exercise BEHAVIORAL

Patients in the PE training group will perform a 12-week online program comprising three 60-minute weekly training sessions. The training program is delivered by certified kinesiologists through a secured online platform. Healthy controls will participate only in the first 2 weeks of PE training.

Active intervention; Healthy controls

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a diagnosis of chronic primary LBP, according to the criteria established by NIH Task Force on Research Standards for CLBP (Deyo et al., 2015). This will be determined by 1) the response to the National Institutes of Health minimum dataset for CLBP (NIH-md), including that LBP has been persistent for at least 3 months or recurrent for at least half of the days in the past 6 months, and 2) the results of a complete case history and physical examination (including functional tasks, quantitative sensory testing, and, if needed, neuro-orthopedic, palpation and range of motion assessments);
• Report a CLBP intensity of at least 4 in a 0-10 numerical rating scale (0 = no pain, 10 = maximum possible pain).
• \- Be over 18 years and under 75 years of age;

You may not qualify if:

• Present any red flags indicative of serious pathology comorbid or as the cause of CLBP (Finucane et al., 2020);
• Have a CLBP phenotype characterized by predominant nociceptive (as in fracture, infection, malignancy, inflammatory or rheumatic spondyloarthropathy, cauda equina syndrome, confirmed by MRI when suspected) or neuropathic pain mechanisms, the latter assessed through score in the DN4 questionnaire (Nijs, et al., 2024);
• Present chronic or acute pain of higher intensity or perceived disability in any other body site than the low back;
• Medical history of diabetes, neurological or psychiatric disorder;
• Presence of significant cardiorespiratory problems or any other potential contraindications to physical exercise as assessed through the Physical Activity Readiness Questionnaire for Everyone (PAR-Q+);
• Following a regular structured PE training program (\>60 min/week) at study's onset, and;
• Presence of any contraindications to MRI examination (including any metallic implants or devices, being pregnant, and claustrophobia).
• Have symptoms or a diagnosis of any acute or chronic pain conditions;
• Medical history of diabetes, neurological or psychiatric disorder;
• Presence of significant cardiorespiratory problems or any other potential contraindications to physical exercise as assessed through the Physical Activity Readiness Questionnaire for Everyone (PAR-Q+);
• Following a regular structured PE training program (\>60 min/week) at study's onset, and;
• Presence of any contraindications to MRI examination (including any metallic implants or devices, being pregnant, and claustrophobia).

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

Montreal General Hospital

Montreal, Quebec, H3H 1V6, Canada

RECRUITING

Related Publications (9)

• Kaplan CM, Kelleher E, Irani A, Schrepf A, Clauw DJ, Harte SE. Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms. Nat Rev Neurol. 2024 Jun;20(6):347-363. doi: 10.1038/s41582-024-00966-8. Epub 2024 May 16.

  PMID: 38755449 BACKGROUND

• Langston PK, Mathis D. Immunological regulation of skeletal muscle adaptation to exercise. Cell Metab. 2024 Jun 4;36(6):1175-1183. doi: 10.1016/j.cmet.2024.04.001. Epub 2024 Apr 25.

  PMID: 38670108 BACKGROUND

• Peake JM, Neubauer O, Della Gatta PA, Nosaka K. Muscle damage and inflammation during recovery from exercise. J Appl Physiol (1985). 2017 Mar 1;122(3):559-570. doi: 10.1152/japplphysiol.00971.2016. Epub 2016 Dec 29.

  PMID: 28035017 BACKGROUND

• Leunig A, Gianeselli M, Russo SJ, Swirski FK. Connection and communication between the nervous and immune systems. Nat Rev Immunol. 2025 Dec;25(12):912-933. doi: 10.1038/s41577-025-01199-6. Epub 2025 Jul 10.

  PMID: 40640567 BACKGROUND

• Bortsov A, Esfahani SJ, Lima LV, Ji RR, Mogil JS, Diatchenko L. How people resolve pain: insights from human transcriptomics into immune activation and therapeutic innovations. Pain. 2025 Nov 1;166(11S):S60-S64. doi: 10.1097/j.pain.0000000000003671.

  PMID: 41086330 BACKGROUND

• Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol. 2014 Apr;14(4):217-31. doi: 10.1038/nri3621. Epub 2014 Feb 28.

  PMID: 24577438 BACKGROUND

• Hayden JA, Ellis J, Ogilvie R, Malmivaara A, van Tulder MW. Exercise therapy for chronic low back pain. Cochrane Database Syst Rev. 2021 Sep 28;9(9):CD009790. doi: 10.1002/14651858.CD009790.pub2.

  PMID: 34580864 BACKGROUND

• Baliki MN, Petre B, Torbey S, Herrmann KM, Huang L, Schnitzer TJ, Fields HL, Apkarian AV. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci. 2012 Jul 1;15(8):1117-9. doi: 10.1038/nn.3153.

  PMID: 22751038 BACKGROUND

• Parisien M, Lima LV, Dagostino C, El-Hachem N, Drury GL, Grant AV, Huising J, Verma V, Meloto CB, Silva JR, Dutra GGS, Markova T, Dang H, Tessier PA, Slade GD, Nackley AG, Ghasemlou N, Mogil JS, Allegri M, Diatchenko L. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Sci Transl Med. 2022 May 11;14(644):eabj9954. doi: 10.1126/scitranslmed.abj9954. Epub 2022 May 11.

  PMID: 35544595 BACKGROUND

MeSH Terms

Conditions

Inflammation; Chronic Pain; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Carlos Gevers Montoro, PhD

CONTACT

+1-8199790448; carlos.geversmontoro@mcgill.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors and data analysts will be blinded to group allocation
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Mechanistic clinical trial in which two patient groups are randomized to two parallel arms (physical exercise vs waitlist), and a group of healthy controls are recruited to compare biological variables.

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 27, 2026
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

CA (1)