Back to resultsThe Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA" (BETA)
Primary Purpose
Low Back Pain
Status
Recruiting
Phase
Phase 3
Locations
Hungary
Study Type
Interventional
Intervention
Tolperisone Hydrochloride
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Low Back Pain focused on measuring back pain, sciatic pain, biomarkers
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,
Sites / Locations
- Department of Neurology, Semmelweis UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tolperisone
Placebo
Arm Description
Tolperisone 3 times 150 mg daily, i.e. a daily dose of 450 mg. Treatment lasts for 14 days
Matching placebo 3 times daily. Treatment lasts for 14 days
Outcomes
Primary Outcome Measures
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)
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)
Secondary Outcome Measures
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
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)
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
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
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
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)
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)
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
Full Information
NCT ID
NCT05544656
First Posted
August 8, 2022
Last Updated
September 15, 2022
Sponsor
Semmelweis University
Collaborators
National Research Develpment and Innovation Fund, Hungary, MEDITOP Pharmaceutical LTD, Hungary
1. Study Identification
Unique Protocol Identification Number
NCT05544656
Brief Title
The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA"
Acronym
BETA
Official Title
The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain -BETA. A Phase 3 Investigator Initiated Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Semmelweis University
Collaborators
National Research Develpment and Innovation Fund, Hungary, MEDITOP Pharmaceutical LTD, Hungary
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low Back Pain
Keywords
back pain, sciatic pain, biomarkers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Single center, randomized double blind study. Randomization is done separately for those with and those without radicular signs.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Randomization is done by non-transparent (opaque) sequentially numbered envelopes, prepared independently from the trial site. The number on the envelope corresponds to the number on the boxes of the trial medication (tolperisone or matching placebo). The envelopes can be opened only at the end of the trial, or in case of emergency. No interim analysis is planned.
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tolperisone
Arm Type
Experimental
Arm Description
Tolperisone 3 times 150 mg daily, i.e. a daily dose of 450 mg. Treatment lasts for 14 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo 3 times daily. Treatment lasts for 14 days
Intervention Type
Drug
Intervention Name(s)
Tolperisone Hydrochloride
Other Intervention Name(s)
EV product code: PRD4558977, miderizone tablet, ATC:M03BX04
Intervention Description
Tolperisone Hydrochloride tablets of 150 mg, administered three times a day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matching placebo administered three times a day
Primary Outcome Measure Information:
Title
Change in the level of biomarkers by the end of the treatment period compared to the pretreatment values.
Description
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)
Time Frame
14 days
Title
Patient reported change in pain features
Description
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)
Time Frame
daily for 14 days
Secondary Outcome Measure Information:
Title
Change in the level of biomarkers enlisted in Primary Outcome 1 in the subgroup of those with ceased or greatly reduced pain
Description
Subgroup analysis of the change in biomarkers restricted to those with ceased or greatly reduced pain
Time Frame
14 days
Title
Change in the intensity of pain by the end of the treatment period
Description
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)
Time Frame
14 days
Title
Change in the level of biomarkers enlisted in Primary Outcome 1 by the end of the treatment period in the tolperisone group
Description
Subgroup analysis of changes in blood, electrophysiological and ultrasound biomarkers by 14 days in the tolperisone group
Time Frame
14 days
Title
Change in the level of paravertebral muscle contraction by the end of the treatment period
Description
Analysis restricted to the electrophysiological and ultrasound biomarkers enlisted in Primary Outcome 1
Time Frame
14 days
Title
Predictive value of the initial levels of biomarkers enlisted in Primary Outcome 1
Description
Evaluation of the association of the initial biomarker values enlisted in Primary Outcome 1 with the 14-day pain features
Time Frame
14 days
Title
Global impression of change by the patient
Description
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)
Time Frame
14 days
Title
Global clinical impression of change (GCI) by the investigator
Description
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)
Time Frame
14 days
Title
Number of participants with treatment-related adverse events
Description
Any adverse events reported during the 14 days of treatment and the 7-day post-treatment period
Time Frame
21 days (14 days treatment plus 7 days post-treatment)
Other Pre-specified Outcome Measures:
Title
Patient reported sleep quality
Description
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).
Time Frame
Daily from 1-14 days
Title
Fingertip-to-floor distance
Description
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.
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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,
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Bereczki, MD,PhD, DSc
Phone
+36 1 2100337
Email
bereczki.daniel@med.semmelweis-univ.hu
First Name & Middle Initial & Last Name or Official Title & Degree
Kitti Dénes, MD
Phone
+3612100337
Email
denes.kitti@med.semmelweis-univ.hu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Bereczki, MD, POhD,DSc
Organizational Affiliation
Semmelweis University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Semmelweis University
City
Budapest
ZIP/Postal Code
H-1083
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Bereczki, MD, PhD, DSc
Phone
+36 1 2100337
Email
bereczki.daniel@med.semmelweis-univ.hu
First Name & Middle Initial & Last Name & Degree
Kitti Dénes, MD
Phone
+36 1 2100337
Email
denes.kitti@med.semmelweis-univ.hu
First Name & Middle Initial & Last Name & Degree
Kitti Dénes, MD
First Name & Middle Initial & Last Name & Degree
Zsuzsanna Arányi, MD, PhD,DSc
First Name & Middle Initial & Last Name & Degree
Nárcisz Tegze, MD
First Name & Middle Initial & Last Name & Degree
Magdolna Simó, MD, PhD
First Name & Middle Initial & Last Name & Degree
Róbert Debreczeni, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA"
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