Immune Response During the Conservative and Minimal Invasive Treatment of Pain Caused by Lumbar Disc Herniation

NCT06545812 | Completed DMC

• 1 other identifier: 2158/97-97-10-24-50
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

Bulging of the intervertebral disc in the lumbar part of the spine is one of the most common degenerative changes of the spine in the elderly population, which causes various symptoms such as radicular pain. Possible mechanisms of radicular pain are mechanical compression of the intervertebral disc on the nerve and sterile local inflammation caused by proinflammatory factors. Depending on the degree of diagnosis, if conservative treatment is not successful, then treatment is focused on minimally invasive methods such as epidural steroid injection (ESI). The achieved neural blockade is believed to alter or interrupt nociceptive input, reflex mechanisms induced by afferent fibers, self-sustaining neuronal activity, and central neuronal activity. On the other hand, corticosteroids reduce inflammation by inhibiting pro-inflammatory mediators and causing a reversible local anesthetic effect. The aim of the research is to measure the concentrations of pro-inflammatory and anti-inflammatory cytokines and metallopeptidases in the serum before physical therapy, i.e. ESI, and two weeks and three months after the start of said therapies, then to examine the clinical status, intensity of pain and limitations of movement associated with pain in all three time points in order to determine the treatment outcomes after the mentioned therapies and examine the possible association of cytokine concentrations with the treatment outcomes and, last but not least, to determine the degree of the patient's psychophysical condition and quality of life before the mentioned therapies, two weeks and three months after the start of the therapies in order to examined possible associations with treatment outcomes and changes in cytokine and metallopeptidases concentrations.

Conditions

Intervertebral Disc Herniation; Back Pain; Analgesic Nephropathy; Inflammatory Response

Keywords

Bulging of intervertebral disc;; Physical therapy;; Epidural steroid injection (ESI);; Pro-inflammatory cytokines;; Anti-inflammatory cytokines;; Metallopeptidases;

Outcome Measures

Primary Outcomes (1)

• Using standard biochemical analyses, measure the concentrations of pro-inflammatory and anti-inflammatory cytokines and metallopeptidases in the serum before physical therapy, i.e. ESI, and two weeks and three months after the start of said therapies.

  There will be changes in the concentrations of pro-inflammatory and anti-inflammatory cytokines and matopeptidases in the serum, like interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (INF-γ), tumor necrosis factor alpha or gamma (TNF-α), chemokine ligand 3 (CCL3) and matrix metalloproteinases MMP-3 and MMP-9, during physical therapy, that is, the minimally invasive application of epidural steroid injection therapy in patients with pain caused by the bulging of the intervertebral disc in the lumbar part of the spine, and whether these changes are expressed when using both methods.

  Up to 3 months

Secondary Outcomes (1)

• Determine the degree of the patient's psychophysical condition and quality of life

  Up to 3 months

Study Arms (2)

Physical therapy for disc herniation

ACTIVE COMPARATOR

Conservative treatment in the form of physical therapy consists of several physical factors, namely laser therapy, ultrasound and transcutaneous electroneurostimulation (TENS). Blood samples for analysis for multicomplex quantitative analysis of anti-inflammatory cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (INF-γ), tumor necrosis factor alpha or gamma (TNF-α), chemokine ligand 3 (CCL3) and matrix metalloproteinases MMP-3 and MMP-9

Device: Physical therapy for disc herniation

Epidural steroid injection (ESI)

ACTIVE COMPARATOR

Minimally invasive methods such as epidural steroid injection (ESI). Blood samples for analysis for multicomplex quantitative analysis of anti-inflammatory cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (INF-γ), tumor necrosis factor alpha or gamma (TNF-α), chemokine ligand 3 (CCL3) and matrix metalloproteinases MMP-3 and MMP-9

Drug: Transforaminal epidural steroid injection

Interventions

Transforaminal epidural steroid injection DRUG

Transforaminal epidural steroid injection (ESI TF) with corticosteroids like Methylprednisolone, Levobupivacaine and Lidocaine according to the protocol of the institution. They reduce inflammation by inhibiting pro-inflammatory mediators and causing a reversible local anesthetic effect.

Also known as: ESI TF

Epidural steroid injection (ESI)

Physical therapy for disc herniation DEVICE

BTL Laser therapy, BTL ultrasound therapy and BTL Transcutaneous electrical nerve stimulation - TENS

Physical therapy for disc herniation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both sexes; age 18-70 years;
• unilateral radicular pain of the lumbar segment;
• diagnosis: intervertebral disc herniation;
• confirmed diagnosis by clinical picture;
• consent to participate in the study, which is confirmed by signing the informed consent;
• unilateral lumbar radicular pain;
• duration of pain up to six months;
• symptomatic disc herniation at one level;
• pain intensity measured by the VAS scale from 0 to 10, which is equal to or greater than 5;
• pain intensity along the leg

You may not qualify if:

• patients younger than 18 or older than 70 years;
• refusal of patients to participate in research;
• patients with systemic, local infections in the area of the lumbar spine;
• dermatological diseases in the area of the lumbar spine;
• pregnancy;
• central stenosis of the lumbar canal;
• patients with bilateral radicular pain;
• lumbar radicular pain caused by causes other than a herniated disc;
• allergy to steroids, local anesthetics, fentanyl, midazolam and contrast media;
• positive history of prolonged bleeding;
• local or systemic infection; previous lumbar spine surgery;
• abuse of opioids;
• proven inflammatory rheumatic disease;
• proven inflammatory bowel disease;
• other infections.

Sponsors & Collaborators

• Josip Juraj Strossmayer University of Osijek: lead

Study Sites (1)

Faculty of Dental Medicine and Health Osijek

Osijek, 31000, Croatia

Location

Related Publications (2)

• Budrovac D, Rados I, Hnatesen D, Harsanji-Drenjancevic I, Tot OK, Katic F, Lukic I, Skiljic S, Neskovic N, Dimitrijevic I. Effectiveness of Epidural Steroid Injection Depending on Discoradicular Contact: A Prospective Randomized Trial. Int J Environ Res Public Health. 2023 Feb 19;20(4):3672. doi: 10.3390/ijerph20043672.

  PMID: 36834367 BACKGROUND

• Rozac K, Matic A, Budrovac D, Hnatesen D, Rados I, Kralik K, Smolic M, Kovac Lukic T. Biological Mechanisms of Pain Management in Lumbar Disk Herniation: Focus on Cytokine Correlations and Therapeutic Approaches. Int J Mol Sci. 2025 Nov 7;26(22):10830. doi: 10.3390/ijms262210830.

  PMID: 41303319 RESULT

Related Links

• Biological Mechanisms of Pain Management in Lumbar Disk Herniation: Focus on Cytokine Correlations and Therapeutic Approaches

MeSH Terms

Conditions

Intervertebral Disc Displacement; Back Pain

Interventions

Physical Therapy Modalities

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Rehabilitation

Study Officials

• Karla Rožac, Master's

  Faculty of Dental Medicine and Health Osijek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: researcher in the doctoral study of Molecular Biosciences, Faculty of dental medicine and health Osijek

Study Record Dates

• First Submitted: July 23, 2024
• First Posted: August 9, 2024
• Study Start: September 2, 2024
• Primary Completion: March 2, 2026
• Study Completion: March 2, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)