The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain BETA

Study Overview
=================
Brief Summary
-----------------
The main purpose of the trial is to identify biomarkers from the blood as well as electrophysiologic and morphometric features (chemical, electrophysiologic and ultrasound biomarkers) that reflect the intensity of pain and/or foretell the efficacy of pharmacological (non-surgical) treatment in patients with acute low back pain.

Detailed Description
-----------------
The investigators include patients aged 18-80 years with acute (less than 1-month) low back pain with or without radicular signs, who do not have severe diseases (abscess, tumor, etc) in the background, already had CT or MRI scan during routine workup, and who have given written consent to participate in the study. Exclusion criteria are pregnancy, hypersensitivity to tolperisone in the history, severe liver or kidney disease, other severe diseases (abscess, tumor, etc) in the background of pain. The patients will be given 3 times daily 150 mg tolperisone or placebo in addition to standard therapy in a randomized double-blind design. Treatment will last for 14 days and a final follow-up is performed at 21 days. Clinical condition and biomarkers will be tested before treatment and at 14 days. Patients fill in a diary on a daily basis.

Official Title
-----------------
The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain -BETA. A Phase 3 Investigator Initiated Study

Conditions
-----------------
Low Back Pain

Intervention / Treatment
-----------------
* Drug: Tolperisone Hydrochloride
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy pain-free volunteers (n=30) outside of the randomized study, will participate to establish normal values of blood biomarkers. Exclusion Criteria: pain, inflammation,

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Single center, randomized double blind study. Randomization is done separately for those with and those without radicular signs.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolperisone<br>Tolperisone 3 times 150 mg daily, i.e. a daily dose of 450 mg. Treatment lasts for 14 days | Drug: Tolperisone Hydrochloride<br>* Tolperisone Hydrochloride tablets of 150 mg, administered three times a day<br>* Other names: EV product code: PRD4558977, miderizone tablet, ATC:M03BX04;|
| Placebo Comparator: Placebo<br>Matching placebo 3 times daily. Treatment lasts for 14 days | Drug: Placebo<br>* matching placebo administered three times a day<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the level of biomarkers by the end of the treatment period compared to the pretreatment values. | Changes in the values of blood biomarkers (nociceptin/orphanin FQ, Met-Enkephalin-Arg6-Phe7 (MEAP), pro-inflammatory cytokines (IL-1β, IL-6, IL-2, IL-8, IL-12, IL-33, CCL3, CXCL1, CCR5, és TNF-α), anti-inflammatory cytokines (IL-10 and IL-4), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins-1b (MIP-1b), platelet-derived growth factor (PDGF AA), vascular endothelial growth factor (VEGF), GM-CSF=granulocyte-macrophage colony-stimulating factor, CGRP (calcitonin gene related peptide), substance P, noradrenalin (norepinephrine), in electrophysiologic markers (quantitative electromyography with surface electrodes in the paravertebral muscles in prone and standing position) and ultrasound markers (bilateral measurements of cross sectional area and antero-posterior diameter of paravertebral muscles in prone and standing position) | 14 days | 
| Patient reported change in pain features | Self evaluation of pain by the patient on a visual scale from zero (no pain at all) to 10 (the most severe pain the patient can imagine) | daily for 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the level of biomarkers enlisted in Primary Outcome 1 in the subgroup of those with ceased or greatly reduced pain | Subgroup analysis of the change in biomarkers restricted to those with ceased or greatly reduced pain | 14 days | 
| Change in the intensity of pain by the end of the treatment period | Self evaluation of pain by the patient on a visual scale from zero (no pain at all) to 10 (the most severe pain the patient can imagine) | 14 days | 
| Change in the level of biomarkers enlisted in Primary Outcome 1 by the end of the treatment period in the tolperisone group | Subgroup analysis of changes in blood, electrophysiological and ultrasound biomarkers by 14 days in the tolperisone group | 14 days | 
| Change in the level of paravertebral muscle contraction by the end of the treatment period | Analysis restricted to the electrophysiological and ultrasound biomarkers enlisted in Primary Outcome 1 | 14 days | 
| Predictive value of the initial levels of biomarkers enlisted in Primary Outcome 1 | Evaluation of the association of the initial biomarker values enlisted in Primary Outcome 1 with the 14-day pain features | 14 days | 
| Global impression of change by the patient | Patient self evaluation of changes by the end of treatment on a 6-grade scale (has become symptom-free; major improvement; minor improvement; no change; minor worsening; major worsening) | 14 days | 
| Global clinical impression of change (GCI) by the investigator | Subjective evaluation of changes by the end of treatment on a 6-grade scale by the investigator (has become symptom-free; major improvement; minor improvement; no change; minor worsening; major worsening) | 14 days | 
| Number of participants with treatment-related adverse events | Any adverse events reported during the 14 days of treatment and the 7-day post-treatment period | 21 days (14 days treatment plus 7 days post-treatment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
back pain, sciatic pain, biomarkers