Identification of Biomarkers and Molecular Targets Involved on Intervertebral Disc Degeneration and Discogenic Pain

NCT06349226 | Recruiting

• 1 other identifier: DISCOLAB
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Low back pain, associated with intrinsic disorders of the spine, is a very frequent clinical condition that is accompanied by high morbidity with effects both on psychosocial aspects, and health care system. It occurs in approximately 80% of the population throughout their lives. Most low back pain is associated with intervertebral disc degeneration (IDD) associated with neuroinflammation and pain. In this context, the study of sphingolipid metabolism can play an important role in the identification of new molecules responsible for the degenerative process. Sphingolipids, in fact, are a class of molecules that are implicated in multiple signal pathways, such as proliferation, degradation of the extracellular matrix, inflammatory state, apoptosis and migration. In particular, sphingosine-1-phosphate (S1P), an intermediate of sphingolipid metabolism, acts as a pro-inflammatory mediator, predominantly in the extracellular environment, regulating important cellular properties related to inflammatory potential and pain. The objective of this study is to characterize the degenerative process in cells isolated from degenerated human intervertebral discs from both at cellular and molecular levels in order to identify new targets implicated in degenerative processes, including sphingolipid signaling pathway.

Conditions

Intervertebral Disc Degeneration; Discogenic Pain; Discogenic Disease

Keywords

intervertebral disc degeneration; discogenic pain; biomarkers; neuroinflammation; iperinnervation; sphingolipids; sphingosine-1 phosphate

Outcome Measures

Primary Outcomes (1)

• Characterization of degenerated intervertebral disc cells

  Determination of a panel of inflammatory and degenerated markers related to components of the extracellular matrix and mediators linked to inflammatory/degenerative processes, hyperinnervation and sphingolipid metabolism.

  through study completion, an average of 3 years

Secondary Outcomes (1)

• Development of cellular model platform

  through study completion, an average of 3 years

Interventions

cell isolation from intervertebral disc tissue and biomarker investigation OTHER

metabolomic, cellular and molecular analysis on intervertebral disc derived cells and investigation of tissue neuroinflammatory and pain-related biomarkers

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who underwent the surgery of discectomy for the degenerative disc.

You may qualify if:

• Patients with disc degeneration for spondylolisthesis, herniated intervertebral disc, and other causes of disc degeneration

You may not qualify if:

• Spinal infection

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

Related Publications (6)

• Marfia G, Guarnaccia L, Navone SE, Ampollini A, Balsamo M, Benelli F, Gaudino C, Garzia E, Fratocchi C, Di Murro C, Ligarotti GK, Campanella C, Landolfi A, Perelli P, Locatelli M, Ciniglio Appiani G. Microgravity and the intervertebral disc: The impact of space conditions on the biomechanics of the spine. Front Physiol. 2023 Mar 14;14:1124991. doi: 10.3389/fphys.2023.1124991. eCollection 2023.

  PMID: 36998982 RESULT

• Navone SE, Campanella R, Guarnaccia L, Ouellet JA, Locatelli M, Cordiglieri C, Gualtierotti R, Gaudino C, Ciniglio Appiani G, Luzzi S, Borsa S, Rampini P, Pluderi M, Haglund L, Riboni L, Alini M, Marfia G. Inflammatory interactions between degenerated intervertebral discs and microglia: Implication of sphingosine-1-phosphate signaling. J Orthop Res. 2021 Jul;39(7):1479-1495. doi: 10.1002/jor.24827. Epub 2020 Aug 24.

  PMID: 32779775 RESULT

• Navone SE, Peroglio M, Guarnaccia L, Beretta M, Grad S, Paroni M, Cordiglieri C, Locatelli M, Pluderi M, Rampini P, Campanella R, Alini M, Marfia G. Mechanical loading of intervertebral disc modulates microglia proliferation, activation, and chemotaxis. Osteoarthritis Cartilage. 2018 Jul;26(7):978-987. doi: 10.1016/j.joca.2018.04.013. Epub 2018 May 1.

  PMID: 29723636 RESULT

• Navone SE, Marfia G, Giannoni A, Beretta M, Guarnaccia L, Gualtierotti R, Nicoli D, Rampini P, Campanella R. Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration. Histol Histopathol. 2017 Jun;32(6):523-542. doi: 10.14670/HH-11-846. Epub 2016 Nov 16.

  PMID: 27848245 RESULT

• Marfia G, Campanella R, Navone SE, Zucca I, Scotti A, Figini M, Di Vito C, Alessandri G, Riboni L, Parati E. Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration. Arthritis Res Ther. 2014 Oct 8;16(5):457. doi: 10.1186/s13075-014-0457-5.

  PMID: 25293819 RESULT

• Marfia G, Navone SE, Di Vito C, Tabano S, Giammattei L, Di Cristofori A, Gualtierotti R, Tremolada C, Zavanone M, Caroli M, Torchia F, Miozzo M, Rampini P, Riboni L, Campanella R. Gene expression profile analysis of human mesenchymal stem cells from herniated and degenerated intervertebral discs reveals different expression of osteopontin. Stem Cells Dev. 2015 Feb 1;24(3):320-8. doi: 10.1089/scd.2014.0282. Epub 2014 Oct 29.

  PMID: 25203751 RESULT

Related Links

• website Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Biospecimen

Retention: SAMPLES WITH DNA

cells from human intervertebral disc

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Intervertebral disc disease; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Marco Locatelli, MD, PhD

  Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurosurgery Unit

  STUDY DIRECTOR

• Mauro Pluderi, MD

  Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurosurgery Unit

  PRINCIPAL INVESTIGATOR

• Giovanni Marfia, MD, PhD

  Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurosurgery Unit, Istituto di Medicina Aerospaziale di Milano, CeMATA - Aeronautica Militare

  STUDY CHAIR

Central Study Contacts

Giovanni Marfia, MD, PhD

CONTACT

0255034268; giovanni.marfia@policlinico.mi.it

Stefania Navone, PhD

CONTACT

0255034268; stefania.navone@policlinico.mi.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: April 5, 2024
• Study Start: May 22, 2018
• Primary Completion: May 21, 2025
• Study Completion: May 21, 2025
• Last Updated: April 5, 2024

Record last verified: 2024-03

Locations

IT (1)