Intervertebral Disc DegenerationNCT06349226
Identification of Biomarkers and Molecular Targets Involved on Intervertebral Disc Degeneration and Discogenic Pain
An observational study of Intervertebral Disc Degeneration and Discogenic Pain, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Intervertebral Disc Degeneration, Discogenic Pain, Discogenic Disease
- What is being tested?
- cell isolation from intervertebral disc tissue and biomarker investigation
- How many people
- 160 participants
- Where
- 1 siteItaly
- Study dates
- 22 May 2018to 21 May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients who underwent the surgery of discectomy for the degenerative disc.
Who may be able to join
- Patients with disc degeneration for spondylolisthesis, herniated intervertebral disc, and other causes of disc degeneration
Who cannot join
- Spinal infection
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
Giovanni Marfia, MD, Phd, 0255035502 ext. +39, giovanni.marfia@policlinico.mi.it
Stefania E Navone, PhD, 0255034268 ext. +39, stefania.navone@policlinico.mi.it
About this study
Official title: Development of New Diagnostic, Prognostic and Therapeutic Strategies in the Field of Degenerative Disc Disease: Identification of Biomarkers and Molecular Targets Involved in Discogenic Pain and Neuroinflammation
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.
Read the detailed description
Low back pain (LBP) is a serious public health problem and has been identified as the most widespread cause of disability worldwide by the 2013 Global Burden of Disease Study. It is estimated that in the Western world the annual incidence of acute low back pain is 5% in adults and that the lifetime prevalence is 80%. Although different anatomical structures can be implicated in the generation of LBP, in many cases this is associated with the degeneration of the intervertebral disc (IVD). IVD degeneration (IDD) represents a chronic age-related process, characterized by a progressive reduction in the content of proteoglycans and water in the nucleus pulposus (NP) with the subsequent loss of the ability of the disc to respond to compressive forces with the possible appearance of instability. Furthermore, this degenerative process is accompanied by the development of a highly inflammatory microenvironment which contributes to exacerbating the degenerative process, leading to the progressive structural failure of the disc itself and in most cases, to pain. From these premises, arises the need to better investigate all the cell-mediated mechanisms underlying IDD, to identify and develop new therapies aimed at recovering the IVD and reducing pain.
In this context, sphingolipids, a class of molecules responsible for multiple signal pathways such as proliferation, migration, apoptosis and angiogenesis, appear to play a key role in exacerbating the inflammatory process and degradation of the extracellular matrix in conditions of IDD. Sphingosine-1-phosphate (S1P) is an intermediate of sphingolipid metabolism, formed from sphingosine through the action of sphingosine kinases (SphK1, SphK2). Increasing evidence suggests that S1P acts as a pro-inflammatory signal, predominantly in the extracellular environment, regulating important cellular properties correlated with the inflammatory potential on chondrocyte-like cells. It has been reported that an alteration in the production and secretion of these molecules is capable of increasing the inflammatory and degenerative condition in various pathologies related to neuroinflammation and pain. The aim of the project is to define new disease biomarkers and 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. Secondary objective is the analysis of the effectiveness of the modulation of sphingolipid metabolism and the in vitro testing of molecules with therapeutic potential.
A greater understanding of the events implicated in the pathogenesis of IDD both at macroscopic and microscopic levels, is of fundamental importance for the development of new diagnostic tools, to be combined with current therapeutic strategies.
- Being tested
- cell isolation from intervertebral disc tissue and biomarker investigation
- Keywords
- intervertebral disc degeneration, discogenic pain, biomarkers, neuroinflammation, iperinnervation, sphingolipids, sphingosine-1 phosphate
- Medical subject headings
- Intervertebral Disc Degeneration, Intervertebral disc disease, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cell isolation from intervertebral disc tissue and biomarker investigationOther
metabolomic, cellular and molecular analysis on intervertebral disc derived cells and investigation of tissue neuroinflammatory and pain-related biomarkers
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: through study completion, an average of 3 years
Secondary outcomes (1)
Development of cellular model platform
Creation of a cellular platform based on patient-derived intervertebral disc cells; assessment of inflammatory and degenerative markers linked to alteration of sphingolipid metabolism; determination of a panel of inflammatory cytokines related to degenerative process, neuro-inflammation and pain; evaluation of prognostic and predictive markers related to disc degeneration.
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2024
- Study start22 May 2018
- Primary completion21 May 2025 (estimated)
- Study completion21 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Intervertebral Disc DegenerationStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marco Locatelli, MD, PhD, Study director, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurosurgery UnitMauro Pluderi, MD, Principal investigator, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurosurgery UnitGiovanni Marfia, MD, PhD, Study chair, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurosurgery Unit, Istituto di Medicina Aerospaziale di Milano, CeMATA - Aeronautica Militare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06349226
- Sponsor's protocol ID
- DISCOLAB
- Status last verified
- Mar 2024
- First submitted
- 21 Mar 2024
- Last updated
- 5 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36998982Navone 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.
PubMed 32779775Navone 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.
PubMed 29723636Navone 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.
PubMed 27848245Marfia 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.
PubMed 25293819Marfia 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.
PubMed 25203751
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of New Diagnostic, Prognostic and Therapeutic Strategies in the Field of Degenerative Disc Disease: Identification of Biomarkers and Molecular Targets Involved in Discogenic Pain and Neuroinflammation
- ClinicalTrials.gov ID
- NCT06349226
- Acronym / sponsor ID
- DISCOLAB
- Keywords
- intervertebral disc degeneration, discogenic pain, biomarkers, neuroinflammation, iperinnervation, sphingolipids, sphingosine-1 phosphate
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- 22 May 2018 (actual)
- Primary completion
- 21 May 2025 (estimated)
- Study completion
- 21 May 2025 (estimated)
- First posted
- 5 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Low back pain (LBP) is a serious public health problem and has been identified as the most widespread cause of disability worldwide by the 2013 Global Burden of Disease Study. It is estimated that in the Western world the annual incidence of acute low back pain is 5% in adults and that the lifetime prevalence is 80%. Although different anatomical structures can be implicated in the generation of LBP, in many cases this is associated with the degeneration of the intervertebral disc (IVD). IVD degeneration (IDD) represents a chronic age-related process, characterized by a progressive reduction in the content of proteoglycans and water in the nucleus pulposus (NP) with the subsequent loss of the ability of the disc to respond to compressive forces with the possible appearance of instability. Furthermore, this degenerative process is accompanied by the development of a highly inflammatory microenvironment which contributes to exacerbating the degenerative process, leading to the progressive structural failure of the disc itself and in most cases, to pain. From these premises, arises the need to better investigate all the cell-mediated mechanisms underlying IDD, to identify and develop new therapies aimed at recovering the IVD and reducing pain.
In this context, sphingolipids, a class of molecules responsible for multiple signal pathways such as proliferation, migration, apoptosis and angiogenesis, appear to play a key role in exacerbating the inflammatory process and degradation of the extracellular matrix in conditions of IDD. Sphingosine-1-phosphate (S1P) is an intermediate of sphingolipid metabolism, formed from sphingosine through the action of sphingosine kinases (SphK1, SphK2). Increasing evidence suggests that S1P acts as a pro-inflammatory signal, predominantly in the extracellular environment, regulating important cellular properties correlated with the inflammatory potential on chondrocyte-like cells. It has been reported that an alteration in the production and secretion of these molecules is capable of increasing the inflammatory and degenerative condition in various pathologies related to neuroinflammation and pain. The aim of the project is to define new disease biomarkers and 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. Secondary objective is the analysis of the effectiveness of the modulation of sphingolipid metabolism and the in vitro testing of molecules with therapeutic potential.
A greater understanding of the events implicated in the pathogenesis of IDD both at macroscopic and microscopic levels, is of fundamental importance for the development of new diagnostic tools, to be combined with current therapeutic strategies.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients who underwent the surgery of discectomy for the degenerative disc.
Key inclusion criteria (1 listed)
- Patients with disc degeneration for spondylolisthesis, herniated intervertebral disc, and other causes of disc degeneration
Key exclusion criteria (1 listed)
- Spinal infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cell isolation from intervertebral disc tissue and biomarker investigationmetabolomic, cellular and molecular analysis on intervertebral disc derived cells and investigation of tissue neuroinflammatory and pain-related biomarkers | Other | – |
Primary outcome
Characterization of degenerated intervertebral disc cells
Time frame: through study completion, an average of 3 years
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.
1 secondary outcome
Development of cellular model platform
Time frame: through study completion, an average of 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2024.
- Results publication: PubMed 36998982Marfia 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.
- Results publication: PubMed 32779775Navone 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.
- Results publication: PubMed 29723636Navone 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.
- Results publication: PubMed 27848245Navone 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.
- Results publication: PubMed 25293819Marfia 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.
- Results publication: PubMed 25203751Marfia 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.
- website Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Locatelli, MD, PhD study director
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurosurgery Unit
Mauro Pluderi, MD principal investigator
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurosurgery Unit
Giovanni Marfia, MD, PhD study chair
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurosurgery Unit, Istituto di Medicina Aerospaziale di Milano, CeMATA - Aeronautica Militare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intervertebral Disc Degeneration and Discogenic Pain, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Marfia, MD, PhD (0255034268 ext. +39, giovanni.marfia@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of degenerated intervertebral disc cells (time frame: through study completion, an average of 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06349226, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2024.