Proteomic and Histological Analysis of Ligamentum Flavum in Lumbar Stenosis

NCT07026552 | Recruiting

• 1 other identifier: ID 7092
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background Lumbar spinal stenosis (LSS) is a common condition characterized by spinal canal narrowing, often linked to ligamentum flavum hypertrophy (LFH) and degeneration. Fibrotic processes involving elastin and collagen alterations contribute to LF thickening and spinal instability. Despite progress, the molecular mechanisms underlying LFH remain unclear, necessitating targeted diagnostic and therapeutic strategies. Objective This study aims to analyze the proteomic and histological changes in LFH associated with LSS, correlating molecular signatures with imaging and surgical findings to identify potential therapeutic targets. Methods LF samples from LSS patients undergoing surgery will be analyzed using mass spectrometry-based proteomics and histology to identify biomarkers and molecular pathways. Correlations between imaging, intraoperative findings, and molecular profiles will be assessed. Expected Results The study aims to identify specific biomarkers and molecular pathways involved in LFH, linking them to clinical and imaging findings. Statistical analyses will evaluate associations between molecular alterations and surgical outcomes to define therapeutic targets. Significance By identifying molecular markers of LFH, this research aims to improve LSS diagnosis and treatment, potentially guiding targeted therapies to slow disease progression and enhance patient outcomes. Study Design A multidisciplinary team from Fondazione Policlinico Universitario Agostino Gemelli and Università Cattolica del Sacro Cuore will conduct the study, ensuring robust data integration and statistical evaluation. Conclusion This comprehensive study will provide valuable insights into the molecular and histological modifications associated with LFH in LSS, paving the way for new therapeutic approaches to improve patient outcomes and satisfaction.

Conditions

Spinal Stenosis of Lumbar Region; Spine Degeneration

Keywords

Lumbar Spinal Stenosis; Ligamentum Flavum Hypertrophy; Proteomic Analysis; Molecular Biomarkers

Outcome Measures

Primary Outcomes (3)

• Histological Modifications in the Ligamentum Flavum in Lumbar Spinal Stenosis and Other Degenerative Spinal Diseases

  This outcome measures the relative abundance and structural organization of collagen and elastin fibers in ligamentum flavum tissue from patients with lumbar spinal stenosis and other degenerative spinal diseases, using histological staining. Unit of Measure: Histological score or percentage composition

  Intraoperative sample collection and subsequent laboratory analysis within 12 months post-surgery

• Cellularity of Ligamentum Flavum Tissue

  This outcome measures the number and density of fibroblasts and other resident cells in the ligamentum flavum. Unit of Measure: Cells per high power field (HPF)

  Intraoperative sample collection; analysis completed within 12 months post-surgery

• Presence of Inflammatory Markers in Ligamentum Flavum

  This outcome evaluates the expression of inflammatory markers (e.g., TNF-α, IL-6, CD68) in ligamentum flavum tissue using immunohistochemistry or immunofluorescence. Unit of Measure: Semi-quantitative histological score or intensity of staining

  Intraoperative sample collection; analysis completed within 12 months post-surgery

Secondary Outcomes (5)

• Expression of Matrix Metalloproteinases (MMPs) in Ligamentum Flavum Tissue

  Within 12 months post-surgery, based on sample processing and analysis.

• Expression of Transforming Growth Factor-beta (TGF-β) in Ligamentum Flavum Tissue

  Intraoperative tissue collection; laboratory analysis within 12 months post-surgery

• Expression of Bone Morphogenetic Proteins (BMPs) in Ligamentum Flavum Tissue

  Intraoperative tissue collection; laboratory analysis within 12 months post-surgery

• Correlation Between Histological and Molecular Findings and Preoperative Clinical Presentation

  Preoperative clinical data and intraoperative sample analysis; correlation analysis within 12 months

• Correlation Between Histological and Molecular Findings and Postoperative Surgical Outcomes

  Intraoperative sample collection and postoperative follow-up at 3, 6, and 12 months

Study Arms (2)

Lumbar Spinal Stenosis Surgery Group

This cohort consists of patients undergoing decompression surgery for lumbar spinal stenosis. Tissue and biological fluid samples will be collected intraoperatively to analyze molecular and histological characteristics associated with ligamentum flavum hypertrophy (LFH).

Other Degenerative Spinal Disease Surgery Group

This cohort includes patients undergoing surgery for other degenerative spinal conditions of the spine such as lumbar disk herniation. Ligamentum flavum samples from this group will serve as a comparative control to assess differences in molecular, histological, and proteomic profiles between non-LFH and LFH tissues.

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of adult patients (aged 50-85 years) undergoing spinal surgery at the Fondazione Policlinico A. Gemelli IRCCS, a tertiary referral center specializing in neurosurgical care. Patients will be evaluated, assessed for surgical indication, and enrolled in the study at the Neurosurgery Department of the Institution.

You may qualify if:

• Radiological (CT and/or MRI) and clinical evidence of lumbar spinal stenosis (LSS).
• Age range: 50-85 years.
• Signed informed consent, medical records release form, and HIPAA authorization form (or equivalent according to local regulations), reviewed and signed by the patient or legally authorized representatives.

You may not qualify if:

• Pediatric population and individuals under 50 years of age.
• Concomitant genetic musculoskeletal disorders.
• History of trauma.
• Spinal infections (spondylodiscitis, osteomyelitis, abscess, etc.).
• Presence of spinal tumors or other neoplasms.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Agostino Gemelli IRCSS

Rome, RM, 00168, Italy

RECRUITING

Related Publications (10)

• Zheng Z, Ao X, Li P, Lian Z, Jiang T, Zhang Z, Wang L. CRLF1 Is a Key Regulator in the Ligamentum Flavum Hypertrophy. Front Cell Dev Biol. 2020 Sep 18;8:858. doi: 10.3389/fcell.2020.00858. eCollection 2020.

  PMID: 33072735 BACKGROUND

• Liu C, Li P, Ao X, Lian Z, Liu J, Li C, Huang M, Wang L, Zhang Z. Clusterin negatively modulates mechanical stress-mediated ligamentum flavum hypertrophy through TGF-beta1 signaling. Exp Mol Med. 2022 Sep;54(9):1549-1562. doi: 10.1038/s12276-022-00849-2. Epub 2022 Sep 21.

  PMID: 36131026 BACKGROUND

• Wang AY, Saini H, Tingen JN, Sharma V, Flores A, Liu D, Olmos M, McPhail ED, Safain MG, Kryzanski J, Arkun K, Riesenburger RI. The Relationship Between Wild-Type Transthyretin Amyloid Load and Ligamentum Flavum Thickness in Lumbar Stenosis Patients. World Neurosurg. 2022 Aug;164:e113-e118. doi: 10.1016/j.wneu.2022.04.008. Epub 2022 Apr 6.

  PMID: 35398327 BACKGROUND

• Zhao R, Dong J, Liu C, Li M, Tan R, Fei C, Chen Y, Yang X, Shi J, Xu J, Wang L, Li P, Zhang Z. Thrombospondin-1 promotes mechanical stress-mediated ligamentum flavum hypertrophy through the TGFbeta1/Smad3 signaling pathway. Matrix Biol. 2024 Mar;127:8-22. doi: 10.1016/j.matbio.2024.01.005. Epub 2024 Jan 26.

  PMID: 38281553 BACKGROUND

• Troyer KL, Puttlitz CM. Nonlinear viscoelasticty plays an essential role in the functional behavior of spinal ligaments. J Biomech. 2012 Feb 23;45(4):684-91. doi: 10.1016/j.jbiomech.2011.12.009. Epub 2012 Jan 10.

  PMID: 22236525 BACKGROUND

• Cheung PWH, Tam V, Leung VYL, Samartzis D, Cheung KM, Luk KD, Cheung JPY. The paradoxical relationship between ligamentum flavum hypertrophy and developmental lumbar spinal stenosis. Scoliosis Spinal Disord. 2016 Sep 5;11(1):26. doi: 10.1186/s13013-016-0088-5. eCollection 2016.

  PMID: 27635416 BACKGROUND

• Lu QL, Wang XZ, Xie W, Chen XW, Zhu YL, Li XG. Macrophage migration inhibitory factor may contribute to hypertrophy of lumbar ligamentum flavum in type 2 diabetes mellitus. Chin Med J (Engl). 2020 Mar 5;133(5):623-625. doi: 10.1097/CM9.0000000000000680. No abstract available.

  PMID: 31996548 BACKGROUND

• Tomkins-Lane CC, Battie MC, Hu R, Macedo L. Pathoanatomical characteristics of clinical lumbar spinal stenosis. J Back Musculoskelet Rehabil. 2014;27(2):223-9. doi: 10.3233/BMR-130440.

  PMID: 24284271 BACKGROUND

• Katz JN, Zimmerman ZE, Mass H, Makhni MC. Diagnosis and Management of Lumbar Spinal Stenosis: A Review. JAMA. 2022 May 3;327(17):1688-1699. doi: 10.1001/jama.2022.5921.

  PMID: 35503342 BACKGROUND

• Sobanski D, Staszkiewicz R, Stachura M, Gadzielinski M, Grabarek BO. Presentation, Diagnosis, and Management of Lower Back Pain Associated with Spinal Stenosis: A Narrative Review. Med Sci Monit. 2023 Feb 23;29:e939237. doi: 10.12659/MSM.939237.

  PMID: 36814366 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Ligamentum Flavum

MeSH Terms

Conditions

Spinal Stenosis

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Giuseppe La Rocca

  Fondazione Policlinico Agostino Gemelli IRCSS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe La Rocca

CONTACT

+ 39 3283776263; giuseppe.larocca@policlinicogemelli.it

Gianluca Galieri

CONTACT

+39 3298803674; gianluca.galieri01@icatt.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 7, 2025
• First Posted: June 18, 2025
• Study Start: June 15, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

IT (1)