The METRIC Study Protocol

Not Applicable

Recruiting

• Conditions: Chronic Low-back Pain
• Interventions: Procedure: lumbar spinal manipulative therapy; Procedure: full spine spinal manipulative therapy; Procedure: sham spinal manipulative therapy

• Registration Number: NCT05986370
• Lead Sponsor: Université du Québec à Trois-Rivières

Brief Summary

The goal of this clinical trial is to test the effects of spinal manipulative therapy in individuals with chronic primary low back pain and determine the neurophysiological mechanisms underlying pain relief. The main questions it aims to answer are: • Is pain relief produced by spinal manipulative therapy in patients with chronic primary low back pain caused by a reduction of C-fiber-related nociceptive processing? • Are these effects greater when spinal manipulative therapy is applied to the whole spine where it is clinically indicated compared with lumbar spine only? • Are these effects greater after 36 treatments over 3 months compared with 12 treatments over 1 month. Participants will receive spinal manipulative therapy (all clinically indicated spine segments or back only) or a control intervention. A group of healthy volunteers will be recruited to assess secondary outcome measures over the same time period, as reference data for comparisons. Researchers will compare the two groups receiving spinal manipulative therapy to the group receiving the control intervention to see if clinical pain relief and the reduction of temporal summation of second pain (produced experimentally) is significantly greater with spinal manipulative therapy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-26
• Study First Submitted QC: 2023-08-02
• Study First Posted: 2023-08-14
• Study Start: 2023-10-25
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-04
• Primary Completion: 2025-09-29
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• Duration of current low back pain (LBP) episode ≥ 6 months;
• Average LBP intensity during the last 7 days ≥ 3/10;
• (For healthy volunteers only) To be of the same sex and age (± 1 year) as a participant with low back pain.

Exclusion Criteria

• Diagnosis of back conditions other than chronic primary LBP e.g., failed back surgery syndrome, spondylosis, spondylolisthesis, spinal stenosis, herniated disc, infection, etc.;
• Presence of pain in another body location that is more severe than the pain in the lower back;
• Presence of a neurological deficit i.e., sensation loss, muscle weakness, decreased deep tendon reflexes;
• Presence of contraindications to spinal manipulative therapy e.g., recent fracture, history of spinal surgery, cauda equina syndrome, inflammatory arthritis, taking anticoagulant medication, active cancer, moderate to severe osteoporosis, abdominal aortic aneurysm;
• Underwent surgery in the last 3 months;
• Pregnancy, ≤ 3 months post-partum or planning to get pregnant in the next 12 months;
• History of spinal manipulative therapy in the past 12 months;
• Scoliosis ≥ 20°;
• BMI ≥ 40;
• Insufficient language skills in French to complete the questionnaires;
• Open or pending litigation for LBP or seeking/receiving disability compensation;
• Diagnosis of an illness affecting the sensorimotor functions e.g., diabetes, multiple sclerosis, amyotrophic lateral sclerosis;
• Diagnosis of mental health disorders (with the exception of anxiety and depression);
• Current drug or alcohol dependence;
• Skin of type I on the Fitzpatrick scale;
• (For healthy volunteers only) Regular use of pain medication or usage in the 48 h prior to data collection;
• (For healthy volunteers only) History of chronic pain;
• (For healthy volunteers only) Acute pain on the days of data collection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lumbar spinal manipulative therapy	lumbar spinal manipulative therapy	Participants will receive spinal manipulative therapy (SMT) exclusively at dysfunctional lumbar segments. Participants will receive 36 SMT sessions over 12 weeks, 3 times per week, each session lasting ≈15 min. Spinal manipulation will be performed using the diversified technique. For each treatment, the SMT provider will perform two spinal manipulations, one on each side of the most painful lumbar vertebra. During spinal manipulations, participants will lay on their side and they will be instructed to inhale and exhale fully before each thrust.
full spine spinal manipulative therapy	full spine spinal manipulative therapy	Participants will receive spinal manipulative therapy (SMT) at dysfunctional spinal segments in the lumbar AND other spine regions. Participants will receive 36 spinal manipulative therapy (SMT) sessions over 12 weeks, 3 times per week, each session lasting ≈15 min. Spinal manipulation will be performed using the diversified technique. For each treatment, the SMT provider will perform a minimum of two spinal manipulations, one on each side of the most painful lumbar vertebra. Spinal manipulation will also be delivered at other dysfunctional spinal segments, based on clinical examination. During spinal manipulations, participants will lay prone, supine or on their side and they will be instructed to inhale and exhale fully before each thrust.
sham spinal manipulative therapy	sham spinal manipulative therapy	Participants will receive 36 sham SMT sessions (3x/week for 12 weeks, each session ≈15 min). This will target dysfunctional segments in the lumbar and other spine regions. Three maneuvers will be used: * Ventral decubitus: 1 to 5 light and brief manual contacts (≈ 20 N and 5 s) will be applied and quickly released over the spinous process of dysfunctional vertebrae identified during clinical examination. * Dorsal decubitus: sections of the treatment table will be slightly raised or lowered (≈ 5 cm) and their lower limbs' position changed once or twice e.g., knees bent, hips internally or externally rotated. Each position maintained during ≈ 30 s. * Lateral decubitus: 1 to 5 impulses at the lowest setting of the Activator V instrument (Activator Methods Int. Ltd., Phoenix, Arizona, USA) will be applied on their gluteus and quadratus lumborum muscles. The position of the instrument will change after each impulse.

Primary Outcome Measures

Name	Time	Method
low back pain intensity	baseline, 1- , 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 26-, 39-, 52- and 64-weeks post-randomization.	In accordance with recommendations for chronic pain trials, participants will be instructed to rate the intensity of their LBP using a numerical rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable). As in the brief pain inventory (BPI), they will be instructed to rate their pain: 1) right now; 2) on average over the last 7 days; 3) at its worst over the last 7 days; 4) at its best over the last 7 days.
temporal summation of second pain	baseline, 4- and 12-weeks post-randomization.	Participants will receive a total of 160 painful laser stimuli, 80 single-pulse stimuli and 80 pulse trains (3 pulses delivered at 0.67 Hz). After each stimulus, participants will be prompted to rate second pain with the display of a numerical pain rating scale. The pain ratings of single pulses will be subtracted from the pain ratings of pulse trains to estimate the intensity of the temporal summation of second pain.

Secondary Outcome Measures

Name	Time	Method
Pressure pain thresholds (PPTs)	baseline, 4- and 12-weeks post-randomization.	PPT will be measured using a handheld digital algometer (Wagner Pain TestTM FPX, Greenwich, Connecticut, USA) and a standardized protocol. The algometer will be applied perpendicularly to the skin of the first test location and the pressure increased at approximately 50 kPa/s until pain is reported by the participant. This procedure will be repeated three times at the same test location. The PPT will be the average of the values obtained during these 3 trials. The same procedures will be repeated at the two other test locations. PPT will be tested on three different body locations: 1) Over the spinous process of the most painful vertebra between L1 and S1; 2) On the right lower limb in the dermatome corresponding to the level of the most painful vertebra; 3) in the center of the right thenar eminence.
low back pain frequency and duration	baseline, 1- , 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 26-, 39-, 52- and 64-weeks post-randomization.	A modified version of the pain frequency-severity-duration scale will be used. Participants will be instructed to answer these 3 questions: * Is the pain recurrent (it comes in episodes) or continuous (it is always present)?; * How many days in the past week have you had low back pain? (0, 1, 2, 3, 4, 5, 6, 7 days; a higher score means a worse outcome); * On average, how many hours per day does the pain last? (0; 1-4; 5-8; 9-12; 13-16; 17-20; 21-24 hours; a higher score means a worse outcome)
C-fiber-related brain responses	baseline, 4- and 12-weeks post-randomization.	Electroencephalography (EEG) will be recorded using a 64-channel BrainVision system with active Ag-AgCl electrodes mounted on an actiCAP, according to the International 10-20 system (Brain Products, Gilching, Germany). Electrodes will be nose-referenced, and the ground will be set at FPz. Signals will be sampled at 500 Hz. Eye movements and blinks will be recorded using electrooculography (EOG). Electrode impedance will be kept below 20 kΩ. Closed eyes resting state EEG will be recorded for 5 min prior to laser stimuli for exploratory EEG analyses. EEG activity will be recorded continuously. The outcome of interest from laser-evoked-brain activity is the response evoked by C-fiber activation. Laser-evoked potentials (LEP) and event-related spectral perturbations (ERSP) will be analyzed using validated methods.
Five times sit-to-stand test	baseline, 4- and 12-weeks post-randomization.	The five times sit-to-stand test will be used as performance based outcome of physical function. Participant sitting on a supported chair will be instructed to stand and sit again as fast as possible, five times in a row. Time will be measured in seconds. The test will be performed twice and the average time for the two trials will be recorded (a higher score means a worse outcome).
Pain catastrophizing	baseline, 4- and 12-weeks post-randomization.	The main elements contributing to the pain experience according to the fear avoidance model of pain will be measured. Pain catastrophizing will be measured with the French-Canadian version of the pain catastrophizing scale (PCS; min = 0, max = 52; a higher score means a worse outcome).
Oswestry Disability Index (ODI)	baseline, 4-, 12-, 26-, 39-, 52- and 64-weeks post-randomization.	Self-reported low back pain related disability will be evaluated using the French-Canadian version of the ODI (0-100%; a higher score means a worse outcome).
Back performance scale (BPS)	baseline, 4- and 12-weeks post-randomization.	The BPS will be used as a performance based outcome of physical function. It includes five daily activities such as putting socks on or picking something on the floor (see PMID: 12444880 for more details). Each activity is rated from 0 to 3, and the five scores are added up (min = 0, max = 15; a higher score means a worse outcome).
Anxiety	baseline, 4- and 12-weeks post-randomization.	Anxiety levels will be measured using the French-Canadian version of the State-Trait Anxiety Inventory, version Y (STAI-Y; min = 20, max = 80; a higher score means a worse outcome).
Patient's global impression of change	After the last treatment session (12-weeks post-randomization)	Participants will be instructed to give their global impression of change on a scale from -100 to 100 (-100 = very much worse, 0 = no change, 100 = very much improved).
Contextual factors (healing encounters and attitudes lists (HEAL))	baseline, 4- and 12-weeks post-randomization.	Contextual factors will be measured using a French adaptation of the healing encounters and attitudes lists (HEAL).
Depression	baseline, 4- and 12-weeks post-randomization.	Depression levels will be measured using the French-Canadian version of the Beck Depression Inventory (BDI; min = 0, max = 63; a higher score means a worse outcome).
Kinesiophobia	baseline, 4- and 12-weeks post-randomization.	The main elements contributing to the pain experience according to the fear avoidance model of pain will be measured. Pain-related fear will be measured with a French adaptation of the Tampa scale for kinesiophobia (TSK; min = 17, max = 68; a higher score means a worse outcome).
Pain vigilance	baseline, 4- and 12-weeks post-randomization.	The main elements contributing to the pain experience according to the fear avoidance model of pain will be measured. Hypervigilance will be measured with a French adaptation of the pain vigilance and awareness questionnaire (PVAQ; min = 0, max = 80; a higher score means a worse outcome).
Expectations of pain relief	baseline and 4-weeks post-randomization.	Participants will be instructed to rate their expectations of pain relief after the treatment on a scale from 0 to 100, 0 being "no relief" and 100 being "complete relief".

Trial Locations

Locations (1)

Université du Québec à Trois-Rivières; 🇨🇦 Trois-Rivières, Quebec, Canada