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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Low Back Pain
• Intervention / Treatment: Drug: Tolperisone Hydrochloride; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Daniel Bereczki, MD,PhD, DSc; Phone Number: +36 1 2100337; Email: bereczki.daniel@med.semmelweis-univ.hu
• Study Contact Backup: Name: Kitti Dénes, MD; Phone Number: +3612100337; Email: denes.kitti@med.semmelweis-univ.hu

Study Locations

• Hungary
  • Budapest, Hungary, H-1083
    • Department of Neurology, Semmelweis University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported sleep quality	Changes in sleep quality reported in patient diary on a 4-grade scale (1: undisturbed sleep; 2: woke up once due to pain; 3: woke up more than once due to pain; 4: could not sleep at all due to pain).	Daily from 1-14 days
Fingertip-to-floor distance	The patient is asked to bend forward and attempt to reach for the floor with their fingertips. The distance between the patient's right long finger and the floor is measured using a standard measuring tape in centimeters.	14 days

Collaborators and Investigators

• Sponsor: Semmelweis University
• Collaborators: National Research Develpment and Innovation Fund, Hungary; MEDITOP Pharmaceutical LTD, Hungary
• Investigators: Principal Investigator: Daniel Bereczki, MD, POhD,DSc, Semmelweis University

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2019
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: biomarkers; back pain; sciatic pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Muscle Relaxants, Central; Tolperisone
• Other Study ID Numbers: LOWBACK-SE-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After trial completion the investigators will be ready to share data with other researchers based on reasonable request.
• IPD Sharing Time Frame: Infinite afer trial completion
• IPD Sharing Access Criteria: request should be discussed by email of the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No