Epigenetic and Molecular Biomarkers in Chronic Low Back Pain and Modic Changes

NCT03406624 | Completed

• 1 other identifier: 2015/697
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 4

Brief Summary

In the present study the investigators aim to examine the presence of bacteria in the disc and Modic Changes (MCs) (bone). A prospective study with 1-year follow-up of two patient populations undergoing elective spinal surgery (spinal fusion or disc herniation surgery) will be conducted. Patients previously operated on at index level will also be included, and evaluated as sub-groups. The following tissues are collected: dermis, sub-fascial tissue, nucleus pulposus, annulus fibrosus, and endplates. Endplate and anular biopsies are only performed in patients undergoing fusion surgery. In addition, air samples from the operating theatre during surgery are collected as negative controls. All tissue samples undergoing culturing should be processed within 4 hours of sampling. The time for sampling and culture processing is noted for each sample. Details are available in a published Method article. For each tissue sample, bacterial growth is recorded and identified at species level. Initially, the microbiologist grades the plates as "no growth", "possible contamination", and "significant growth". Possible contamination means that the bacteria may be derived from the environment and can be introduced at any step from the sample is taken to the analyses in the laboratory. The investigators will perform direct 16S rDNA nanopore sequencing on all frozen tissue samples and air samples. Other broad metagenomic methods may be considered, e.g., Illumina sequencing. Since Cutibacterium acnes is considered the main pathogen in this setting, the investigators will also use a specific quantitative PCR on all samples. In addition, the investigators will use whole genome sequencing on C. acnes isolates for phylogenetic analyses to compare isolates found in different samples from the same patient. Based on cultivation alone, samples will be graded as "significant growth", "possible contamination" or "no growth". Before unblinding, in preparation for the sensitivity analyses, "possible contamination" will be classified into a final categorization of "possible significant growth" or "no growth" based on PCR". In cases of a culture-negative nanopore-positive biopsy, the sample is classified as no growth when we find the same bacterial species in the air control sample as in the biopsy. Since the study was designed and the method article was prepared, nanopore sequencing technology has become available and incorporated into the present analysis. Although not part of the original protocol, nanopore sequencing was applied to the samples to complement the diagnostic approach. The results derived from nanopore sequencing will be included as part of prespecified sensitivity analyses to evaluate the robustness of the main finding. These analyses allow assessment of whether the inclusion of sequencing-based detection influences the overall estimates and conclusions, while maintaining the original study design. The microbiologists, the pathologist, statistician and clinicians are blinded until end of study. Blood-samples are collected to characterize gene expression patterns and related markers.

Conditions

Low Back Pain

Keywords

Modic changes; biomarkers; low back pain

Outcome Measures

Primary Outcomes (3)

• Microbiological analysis (aerob, anaerob cultivation)

  During surgery

• Histopathology and PCR

  During surgery

• Gene expression profiling

  During surgery

Secondary Outcomes (7)

• Oswestry disability index

  Pre surgery, 3 and 12 months postoperatively

• Roland and Morris Disability Questionnaire

  Pre surgery, 3 and 12 months postoperatively

• Low back pain

  Pre surgery, 3 and 12 months postoperatively

• Leg pain

  Pre surgery, 3 and 12 months postoperatively

• Health-related quality of life (EQ-5D)

  Pre surgery, 3 and 12 months postoperatively

Study Arms (4)

Spinal fusion with modic changes

Patients scheduled for surgery with lumbar spinal fusion with procedures involving moderate to extensive removal of the disc, and with modic changes seen on MRI at the actual level for surgery

Procedure: Biopsy

Spinal fusion without modic changes

Patients scheduled for surgery with lumbar spinal fusion with procedures involving moderate to extensive removal of the disc, but with no modic changes seen on MRI at the actual level for surgery

Procedure: Biopsy

Disc herniation surgery with modic changes

Patients scheduled for disc herniation surgery, and with modic changes seen on MRI at the actual level for surgery

Procedure: Biopsy

Disc herniation surgery without modic changes

Patients scheduled for disc herniation surgery, but with no modic changes seen on MRI at the actual level for surgery

Procedure: Biopsy

Interventions

Biopsy PROCEDURE

Biopsies will be taken from disc and / or endplates during elective lumbar fusion surgery or disc herniation surgery (endplate biopsy is omitted in disc herniation surgery)

Disc herniation surgery with modic changes; Disc herniation surgery without modic changes; Spinal fusion with modic changes; Spinal fusion without modic changes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from orthopaedic outpatient clinics at four university hospitals. They will be asked for participation after being scheduled for surgery with lumbar spinal fusion with procedures involving moderate to extensive removal of the disc (i.e. transforaminal lumbar interbody fusion (TLIF), posterior Lumbar Interbody Fusion (PLIF)) or or disc herniation surgery.

You may qualify if:

• Patients scheduled for surgery with lumbar spinal fusion with procedures involving moderate to extensive removal of the disc or disc herniation surgery (for cases: MC seen on MRI at the actual level for surgery, for controls: no MC seen on MRI at the actual level for surgery)
• LBP in the area below the 12th rib and above the gluteal folds
• Age \> 18 years
• Written informed consent

You may not qualify if:

• Antibiotic treatment within the preceding one month before surgery
• Use of glucocorticoids the preceding month before surgery
• Small dots (i.e. \<= 5 mm or height \<10% of vertebra) are not included for any cases or control group
• Unwilling to participate
• Contraindications to MRI

Sponsors & Collaborators

• Oslo University Hospital: lead
• Haukeland University Hospital: collaborator
• University Hospital, Akershus: collaborator
• Helse Stavanger HF: collaborator

Study Sites (4)

Haukeland University Hospital

Bergen, Bergen, 5021, Norway

Location

Akershus University Hospital

Lørenskog, Lørenskog, 1478, Norway

Location

Oslo University Hospital Ullevål

Oslo, Oslo County, 4950, Norway

Location

Stavanger Universitetssjukehus

Stavanger, Norway

Location

Related Publications (1)

• Rolfsen MP, Gammelsrud KW, Espeland A, Braten LC, Mjones SB, Austevoll I, Dolatowski FC, Arrestad MB, Toppe MK, Orlien IE, Holberg-Petersen M, Fagerland M, Zwart JA, Storheim K, Hellum C. Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study. BMJ Open. 2024 May 6;14(5):e082244. doi: 10.1136/bmjopen-2023-082244.

  PMID: 38719329 DERIVED

MeSH Terms

Conditions

Low Back Pain

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Smeland, Professor

  Oslo University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of FORMI

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: January 23, 2018
• Study Start: January 29, 2018
• Primary Completion: April 3, 2026
• Study Completion: April 3, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NO (4)