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

Phase 3

Active, not recruiting

• Conditions: Low Back Pain
• Interventions: Drug: Placebo; Drug: Tolperisone Hydrochloride

• Registration Number: NCT05544656
• Lead Sponsor: Semmelweis University

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.

Study Timeline

• Study Start: 2019-12-13
• Study First Submitted: 2022-08-08
• Study First Submitted QC: 2022-09-15
• Study First Posted: 2022-09-16
• Primary Completion: 2023-12-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-16
• Last Update Posted: 2024-04-17
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 150

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,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo 3 times daily. Treatment lasts for 14 days
Tolperisone	Tolperisone Hydrochloride	Tolperisone 3 times 150 mg daily, i.e. a daily dose of 450 mg. Treatment lasts for 14 days

Primary Outcome Measures

Name	Time	Method
Change in the level of biomarkers by the end of the treatment period compared to the pretreatment values.	14 days	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)
Patient reported change in pain features	daily for 14 days	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)

Secondary Outcome Measures

Name	Time	Method
Change in the level of biomarkers enlisted in Primary Outcome 1 in the subgroup of those with ceased or greatly reduced pain	14 days	Subgroup analysis of the change in biomarkers restricted to those with ceased or greatly reduced pain
Change in the intensity of pain by the end of the treatment period	14 days	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)
Change in the level of biomarkers enlisted in Primary Outcome 1 by the end of the treatment period in the tolperisone group	14 days	Subgroup analysis of changes in blood, electrophysiological and ultrasound biomarkers by 14 days in the tolperisone group
Change in the level of paravertebral muscle contraction by the end of the treatment period	14 days	Analysis restricted to the electrophysiological and ultrasound biomarkers enlisted in Primary Outcome 1
Predictive value of the initial levels of biomarkers enlisted in Primary Outcome 1	14 days	Evaluation of the association of the initial biomarker values enlisted in Primary Outcome 1 with the 14-day pain features
Global impression of change by the patient	14 days	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)
Global clinical impression of change (GCI) by the investigator	14 days	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)
Number of participants with treatment-related adverse events	21 days (14 days treatment plus 7 days post-treatment)	Any adverse events reported during the 14 days of treatment and the 7-day post-treatment period

Trial Locations

Locations (1)

Department of Neurology, Semmelweis University; 🇭🇺 Budapest, Hungary