Cytokines, Neuroplasticity Modulators, and Biomarkers in Spinal Canal Stenosis and Endoscopic Decompression

NCT07232836 | Not Yet Recruiting

• 1 other identifier: PoznanUPhyEd no. 5
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Research Rationale and Study Design Lumbar spinal stenosis (LSS) is a common degenerative musculoskeletal disorder characterized by narrowing of the spinal canal, often leading to pain and disability. One of the primary contributors to this condition is hypertrophy (thickening) of the ligamentum flavum (LF), along with facet joint degeneration, intervertebral disc herniation, and ligament ossification. However, the pathophysiological mechanisms behind these changes remain incompletely understood. Histological changes in hypertrophied LF include fibrocartilaginous metaplasia, type II collagen proliferation, ossification, calcium crystal deposition, and degeneration of elastic and collagen fibers. Both mechanical stress and inflammatory processes, particularly macrophage infiltration, are considered key contributors to degeneration, especially in the aging population. Yet, inflammation linked to systemic metabolic disorders-such as obesity and sarcopenia-may also significantly influence the degeneration of spinal structures. Metabolic Inflammation and the Role of Adipokines Recent research has highlighted the role of adipokines in the pathogenesis of degenerative spinal and joint diseases. Disrupted lipid metabolism and chronic low-grade inflammation contribute to tissue remodeling, extracellular matrix (ECM) degradation, and ectopic fat deposition in spinal structures. Epidural fat, normally present in the spinal canal, can become inflamed and secrete pro-inflammatory cytokines, potentially affecting adjacent tissues such as muscles and ligaments. Conditions like spinal epidural lipomatosis, which is associated with obesity, exemplify this pathological mechanism. While adipokines like leptin and visfatin have been previously associated with LF ossification and degeneration, the presence and role of others-such as adipsin, vaspin, resistin, lipocalin-2, progranulin, chemerin, omentin-1, and GDF-15-have not yet been studied in LF or epidural fat. Given their known effects on inflammation and ECM remodeling, these molecules are strong candidates for involvement in spinal canal narrowing. Research Hypotheses and Objectives This study hypothesizes that adipose tissue-derived cytokines, particularly from epidural fat, contribute to LF degeneration and LSS through inflammatory and metabolic signaling. The main research objectives are to:

• 100 patients undergoing lumbar spine surgery at the Orthopaedic-Rehabilitation Clinical Hospital in Poznań: o 50 with LSS (ages 40-90)
• 50 with disc herniation only (ages 18-40; control group) Tissue collection (intraoperative):
• Ligamentum flavum
• Paraspinal muscles
• Epidural adipose tissue Blood samples:
• Collected from all participants: o Within 48 hours before surgery o Two months post-surgery Clinical assessments:
• Disability and pain scales
• Preoperative MRI scans Laboratory analysis:
• Molecular testing:
• mRNA expression of selected cytokines and adipokines using PCR
• Protein levels determined via ELISA in both serum and tissue homogenates • Cell culture studies:
• One-third of collected tissue is used to establish primary cell cultures from LF, paraspinal muscles, and epidural fat
• Cells will be stimulated with conditioned media from epidural fat and with selected recombinant cytokines (e.g., vaspin, lipocalin-2, GDF-15)
• Experiments will assess the gene and protein expression of key molecules involved in inflammation, ECM remodeling, bone metabolism, fibrosis, and matrix degradation. The goal is to clarify the local and systemic roles of adipokines and inflammation in the pathogenesis of LF hypertrophy and LSS. This knowledge may aid in identifying biomarkers for disease progression and therapeutic targets for non-surgical interventions in the future.

Conditions

Spinal Stenosis; Ligamentum Flavum Hypertrophy

Keywords

adipokines; biomarkers; endoscopic spinal canal decompression; inflammation; epidural adipose tissue

Outcome Measures

Primary Outcomes (2)

• Adipokines concentration in the epidural adipose tissue, paraspinal muscles, ligamentum flavum and blood.

  Day 0 and Month 2

• Neuroplasticity modulators concentration in the epidural adipose tissue, paraspinal muscles, ligamentum flavum and blood.

  Day 0 and Month 2

Secondary Outcomes (5)

• Low back pain on visual analogue scale

  Day 0 and Month 2

• Oswestry Disability Index

  Day 0 and Month 2

• Thickness of the ligamentum flavum

  Before intervention

• Diameter of the spinal canal

  Before intervention.

• Schizas Scale

  Before intervention.

Study Arms (3)

Spinal Stenosis

EXPERIMENTAL

Procedure: Endoscopic Spinal Canal Decompression

No Spinal Stenosis

NO INTERVENTION

Tissues collected during surgery from people without spinal stenosis.

No intervention

NO INTERVENTION

Interventions

Endoscopic Spinal Canal Decompression PROCEDURE

Patients from the study group will undergo endoscopic decompression of the spinal canal, which involves the removal of tissues (bone, ligament, joint) causing compression of the neural structures of the spine and the possible removal of an abnormally displaced fragment of the intervertebral disc.

Spinal Stenosis

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Spinal stenosis in the lumbar spine with a referral for surgical treatment using endoscopic spinal decompression.
• Age: 40-90 years.
• Current MRI results.
• Consent to participate in the study.
• Intervertebral disc herniation in the lumbar spine with a referral for surgical treatment using endoscopic discectomy.
• Age: 18-40 years.
• Current MRI results.
• Consent to participate in the study.

You may not qualify if:

• History of:
• rheumatoid arthritis of the intervertebral joints,
• joint pain located elsewhere if it is more severe than the pain caused by stenosis,
• pathologies and/or medications that may disturb the balance between pro- and anti-inflammatory factors (e.g. inflammatory diseases, rheumatoid arthritis, ankylosing spondylitis, acute infection),
• uncontrolled diabetes, poorly controlled hypertension, clinically significant liver function impairment, acute coronary event, unstable angina pectoris, symptoms of heart failure, pacemaker implantation,
• neurological diseases within the last 6 months,
• previous spine surgery at the lumbar level,
• mechanical injuries to the spine after an accident,
• advanced osteoporosis,
• pregnancy, lactation.

Sponsors & Collaborators

• Poznan University of Physical Education: lead
• Poznan University of Medical Sciences: collaborator

Related Publications (9)

• Tarabeih N, Shalata A, Trofimov S, Kalinkovich A, Livshits G. Growth and differentiation factor 15 is a biomarker for low back pain-associated disability. Cytokine. 2019 May;117:8-14. doi: 10.1016/j.cyto.2019.01.011. Epub 2019 Feb 15.

  PMID: 30776685 BACKGROUND

• Fujita N, Hosogane N, Hikata T, Iwanami A, Watanabe K, Shiono Y, Okada E, Ishikawa M, Tsuji T, Shimoda M, Horiuchi K, Nakamura M, Matsumoto M, Ishii K. Potential Involvement of Obesity-Associated Chronic Inflammation in the Pathogenesis of Idiopathic Spinal Epidural Lipomatosis. Spine (Phila Pa 1976). 2016 Dec 1;41(23):E1402-E1407. doi: 10.1097/BRS.0000000000001646.

  PMID: 27105459 BACKGROUND

• Xiang Q, Wu Z, Zhao Y, Tian S, Lin J, Wang L, Jiang S, Sun Z, Li W. Cellular and molecular mechanisms underlying obesity in degenerative spine and joint diseases. Bone Res. 2024 Dec 11;12(1):71. doi: 10.1038/s41413-024-00388-8.

  PMID: 39658574 BACKGROUND

• Endo T, Koike Y, Hisada Y, Fujita R, Suzuki R, Tanaka M, Tsujimoto T, Shimamura Y, Hasegawa Y, Kanayama M, Yamada K, Iwata A, Sudo H, Ishii M, Iwasaki N, Takahata M. Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity. Global Spine J. 2023 Jun;13(5):1325-1331. doi: 10.1177/21925682211031514. Epub 2021 Oct 6.

  PMID: 34615403 BACKGROUND

• Zhang H, Hong Z, Jiang Z, Hu W, Hu J, Zhu R. miR-29b-3p Affects the Hypertrophy of Ligamentum Flavum in Lumbar Spinal Stenosis and its Mechanism. Biochem Genet. 2025 Apr;63(2):1824-1838. doi: 10.1007/s10528-024-10811-8. Epub 2024 Apr 16.

  PMID: 38625592 BACKGROUND

• Furusawa N, Baba H, Maezawa Y, Uchida K, Wada M, Imura S, Fukuda M. Calcium crystal deposition in the ligamentum flavum of the lumbar spine. Clin Exp Rheumatol. 1997 Nov-Dec;15(6):641-7.

  PMID: 9444420 BACKGROUND

• Szpalski M, Gunzburg R. Lumbar spinal stenosis in the elderly: an overview. Eur Spine J. 2003 Oct;12 Suppl 2(Suppl 2):S170-5. doi: 10.1007/s00586-003-0612-1. Epub 2003 Sep 9.

  PMID: 13680315 BACKGROUND

• Silwal P, Nguyen-Thai AM, Alexander PG, Sowa GA, Vo NV, Lee JY. Cellular and Molecular Mechanisms of Hypertrophy of Ligamentum Flavum. Biomolecules. 2024 Oct 10;14(10):1277. doi: 10.3390/biom14101277.

  PMID: 39456209 BACKGROUND

• Carregaro RL, Tottoli CR, Rodrigues DDS, Bosmans JE, da Silva EN, van Tulder M. Low back pain should be considered a health and research priority in Brazil: Lost productivity and healthcare costs between 2012 to 2016. PLoS One. 2020 Apr 1;15(4):e0230902. doi: 10.1371/journal.pone.0230902. eCollection 2020.

  PMID: 32236113 BACKGROUND

MeSH Terms

Conditions

Spinal Stenosis; Inflammation

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marzena Ratajczak, PhD

  Poznan University of Physical Education

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marzena Ratajczak, PhD

CONTACT

+48 604773816; mratajczak@awf.poznan.pl

Piotr Krutki, Prof.

CONTACT

+48 618355439; krutki@awf.poznan.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 25, 2025
• First Posted: November 18, 2025
• Study Start: November 17, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available once the investigation is completed.
• Access Criteria: Anonymised patient data may be transferred to the database in justified cases and at the request of the person concerned.