Mechanisms of Chiropractic Spinal Manipulation for Chronic Low Back Pain

Study Overview
=================
Brief Summary
-----------------
This is a mechanistic randomized controlled trial on the effects of chiropractic spinal manipulative therapy on patients with chronic low back pain. It is designed as a mechanistic trial, in which the main objective is to identify which variables related to central sensitization can help predict the response to spinal manipulation, and the evolution of which of these variables can help explain clinical changes in chronic low back pain patients receiving spinal manipulative therapy.

Detailed Description
-----------------
The study is a mechanistic randomized controlled trials on the effects of chiropractic spinal manipulative therapy on patients with chronic low back pain. 100 chronic low back pain patients will be randomly allocated to receive 12 sessions over 4 weeks of spinal manipulative therapy or placebo spinal manipulation. The main objective is to identify variables related to a central sensitization or nociplastic pain phenotype can help predict the response to spinal manipulation. Additionally, changes in these variables during the treatment period will be used to identify potential pain mechanisms involved in pain relief by spinal manipulation. An additional group of 50 healthy volunteers will be used to measure the same variables and their evolution during 4 weeks in a healthy control population. Response to treatment will be measured according to changes in pain intensity and disability.

Official Title
-----------------
Efficacy of Chiropractic Spinal Manipulative Therapy in Patients With Primary Chronic Low Back Pain: a Mechanistic Randomized Controlled Trial

Conditions
-----------------
Chronic Low-back Pain

Intervention / Treatment
-----------------
* Other: Spinal Manipulation
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Healthy volunteers will be accepted for that specific comparison group. Those volunteers must demonstrate no evidence of any systemic pathology, inflammatory, psychiatric, neurological or pain condition. Inclusion Criteria: diagnosis of primary chronic low back pain (performed in the initial evaluation or previously received by a healthcare professional), with or without leg pain minimum of three months of duration Exclusion Criteria: diagnosis of neuropathic pain in the lower extremity evidence of specific pathology affecting the lumbar spine diagnosis of psychiatric disorder or pain disorder affecting the hand/thumb or in the vicinity of the lumbar area intake corticosteroids, opioids or anticytokine medications pregnancy having been treated with spinal manipulation in the previous 12 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo-controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spinal manipulation<br>Group receiving 12 sessions of spinal manipulative therapy in the lumbar area | Other: Spinal Manipulation<br>* Manual therapy technique applied by a chiropractor in the form of a high-velocity low-amplitude force to the lumbopelvic spine<br>|
| Placebo Comparator: Placebo<br>Group receiving 12 sessions of placebo spinal manipulative therapy in the lumbar area | Other: Placebo<br>* Placebo spinal manipulation consisting in the application by a chiropractor of a lower-velocity lower-amplitude force to gluteal muscles in a non-intentional direction<br>|
| No Intervention: Healthy controls<br>A healthy control population will receive no treatment during the same time period (4 weeks) to measure the same physiological variables and their evolution. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Pain intensity will be measured by showing patients a numerical rating scale from 0 (no pain at all) to 100 (maximum possible pain), and patients will rate with a number their current pain, highest, lowest and average during the 7 previous days (baseline) or the days following the previous session. | 4 weeks | 
| Oswestry Low Back Pain Disability Index | The Oswestry Disability Index (ODI) questionnaire provides the level of self-reported disability in activities of daily living (ADL) related to low back pain. It includes 10 items rated on a Likert scale from 0-5. The total range of possible scores is from 0-50, where 0 means no disability at all, and 50 is the maximal disability. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Catastrophizing Scale | The Pain Catastrophizing Scale (PCS) provides the level of catastrophizing beliefs and emotions that a person has with regards to his/her own pain experience, in this case, low back pain. It includes 13 items rated on a Likert scale from 0-4. The total range of possible scores is from 0-52, where 0 is the lowest possible level of catastrophizing and 52 the highest. This scale will also be used in healthy participants. | 4 weeks | 
| Central Sensitization Inventory | The Central Sensitization Inventory (CSI) identifies key symptoms associated with central sensitization and provides a quantification for the degree of these symptoms, which help to identify a central sensitization phenotype patients with chronic pain. It includes 25 items rated on a Likert scale from 0-4. The total range of possible scores is from 0-100, where 0 is the lowest possible level of central sensitization symptoms and 100 the highest. Additionally, the CSI asks one more question related to the previous diagnosis of either one of 10 conditions that have been related to central sensitization. this part is informative and is not used for scoring purposes. This scale will also be used in healthy participants. | 4 weeks | 
| Pressure pain thresholds | Pressure pain thresholds (PPTs) are part of quantitative sensory testing. The aim is to identify the threshold and the sensitivity to suprathreshold pressure stimulation in different areas of the patients' bodies. A digital algometer will be used (Wagner Force Dial FPX, Greenwich, CT, USA) to measure PPTs in the lumbar segment of greatest pain for each patient (2cm lateral to the spinous process or the posterosuperior iliac spine if applicable) locally, in the dermatome of this segment in the lower limbs, at the regional level four segments cranial from the segment of greatest pain, and remotely at the level of the thenar eminences. Measures will always be taken bilaterally two times, and averaged. At that time, the patient will rate in a numerical rating scale from 0 to 100 the intensity of the first painful stimulation (suprathreshold sensitivity). For healthy participants, pressure pain thresholds will be measured at every segment of the lumbar spine and in the thenar eminences. | 4 weeks | 
| Urinary levels of cytokine Tumor Necrosis Factor alpha | Tumor Necrosis Factor alpha (TNF-a) is a pro-inflammatory cytokines that have been involved with different stages of low back pain. First morning urine samples will be taken from patients and healthy participants at the beginning and the end of the trial period. Samples will be stored at -20ºC and concentrations will be measured with a sandwich ELISA. TNF-a will be the only cytokine used for before and after changes. | 4 weeks | 
| Beck Depression Inventory II | The Beck Depression Inventory (BDI-II) identifies key symptoms associated with clinical depression and provides a quantification for the presence and severity of depressive symptoms. It includes 21 items rated on a Likert scale from 0-3. The total range of possible scores is from 0-63, where 0 is the lowest possible level of depressive symptoms and 63 the highest.This scale will also be used in healthy participants. | 4 weeks | 
| Generalized Anxiety Disorder scale | The Generalized Anxiety Disorder (GAD) identifies key symptoms associated with generalized anxiety disorder and provides a quantification for the presence and severity of these symptoms. It includes 7 items rated on a Likert scale from 0-3. The total range of possible scores is from 0-63, where 0 is the lowest possible level of depressive symptoms and 21 the highest. The threshold of 10/21 is used to diagnose generalized anxiety disorder. This scale will also be used in healthy participants. | 4 weeks | 
| Expectations of pain relief | Participants will rate in a numerical rating scale their expectations of pain relief at the end of the trial. It will consist on a scale from -100 (maximum reduction in current pain) to 0 (no change) to +100 (maximum imaginable pain increase). | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic low back pain, Spinal manipulation, Central sensitization, Pressure pain thresholds, Cytokines, Chiropractic