OsteoarthritisNCT02565160
Analysis of Human Knee Joint Fluid Using Metabonomic, Genomic and Tribology Techniques
An observational study of Osteoarthritis and Septic Arthritis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Making the diagnosis underlying a painful, swollen joint currently involves aspiration followed by numerous microbiological and biochemical laboratory tests. This can be costly, time consuming and in the case of an acutely swollen joint, lead to a lengthy inpatient admission. Read more about this study
- Who is it for?
- Ages 16 to 90 years
- Conditions the study is for
- Osteoarthritis, Septic Arthritis, Rheumatoid Arthritis
- What is being tested?
- Intra-articular aspiration of Joint, Joint irrigation washout and Total Joint Arthroplasty
- Type of treatment
- Surgery or procedure
- How many people
- 150 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2015to Oct 2021
- 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 16 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: In summary we expect to recruit 150 subjects and sample three body fluid types. In some cases control and multiple time points will be collected.
Who may be able to join
- The patients will be recruited in several scenarios.
- Anyone receiving a diagnostic aspirate of joint.
- Patients undergoing joint arthroscopy
- Patients undergoing joint replacement
- Patients undergoing prosthetic joint revision surgery
Who cannot join
- No patient under 16 years or age or older than 80 years will be entered for the study.
- Any female patient who is pregnant will be excluded.
- Any patient medicated with anti-coagulants will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Looking for Biomarkers in Human Joint Fluid Using Metabonomic, Microbiomic and Tribological Analysis
Making the diagnosis underlying a painful, swollen joint currently involves aspiration followed by numerous microbiological and biochemical laboratory tests. This can be costly, time consuming and in the case of an acutely swollen joint, lead to a lengthy inpatient admission. There is an unmet need to provide a quick, easy, reliable dipstick like test to analyse joint fluid in the community, clinic, or emergency department setting.
The investigators aim to use well established metabonomic techniques to:
- Analyse fluid from patients with swollen joints
- Identify potential biomarkers of inflammatory, infective and osteoarthritic causes of joint swelling
- Correlate this with lubrication and wear properties of the fluid The long term goal is to develop time saving, cost effective, non-invasive diagnostic tests to improve management of a swollen joint. The biomedical research centre at Imperial provides a unique and unparalleled clinical and scientific environment to conduct this research. The Imperial College division of Computational and Systems Medicine has an international reputation in metabonomics and this, together with the high volume of patients with swollen joints treated at Imperial National Health Service Trust (c1000/yr) ensures that the study can take place in an environment conductive to success.
Read the detailed description
Swollen joints represent a diagnostic challenge. Possible diagnoses include: osteoarthritis, gout, rheumatological disease or infection. Diagnostic methods are limited to microscopy, microbiology and trace analysis. These methods can be slow, time consuming, expensive and often inconclusive.
Osteoarthritis varies in the severity of any inflammatory response and subsequent symptoms. To date no molecular link has been established to explain this ambiguity. Previous studies have identified metabolites of the inflammatory response but failed to investigate any correlation with symptoms or response to targeted injections.
Microbial infections of joints are destructive. It typically takes 2-3 days to identify a causative organism and confirm diagnosis. Recent studies suggest low-level bacterial colonisation within joints. The investigators aim to analyse the joint fluid for any bacterial colonisation using enrichment and 16S Polymerase Chain Reaction (PCR) then correlate the results to the metabolic profile. In addition the investigators aim to seek metabolites indicative of the presence of a biofilm which, if present severely limits treatment options.
Metabonomics is the quantitative measurement of the dynamic multiparametric response of a living system to pathophysiological stimuli or genetic modification. This provides a global metabolic profile despite a complex biological sample and has proven useful in many fields.
Our hypotheses are:
- Each pathology will have a unique metabolic profile
- Inflammatory osteoarthritis will contain a different metabolic profile and potentially biomarkers to treatment and/or response
- Specifically the presence and detection of organism sub-type and biofilm biomarkers
- These profiles can be characterised by analysis of blood, urine and joint fluid
- This data can be used to generate diagnostic tests that will aid management of a swollen joint.
- There will be a correlation between metabolic profile and lubricant properties of the joint fluid, that can be utilised in future engineering strategies to manage osteoarthritis.
- To analyse joint fluid from osteoarthritic joints to identify potential biomarkers of the disease and further understanding of the cartilage destruction pathways 2. To assess population variances in joint fluid composition using metabonomics and whether this composition correlates to arthropathy of joints 3. To study the lubrication and wear properties of the joint fluid and understand how the metabolic profile influences lubrication and subsequently joint wear.
- To study joint fluid using metabonomics to identify biomarkers of bacterial colonisation in tandem with microbial 16S Polymerase Chain Reaction and genomic sequencing.
Project Timeline:
Phases of the project are to be as follows:
Full research, Site and Ethical Approval: Provisional ethics is already granted. No obstacles to research and site approval are expected and this should be achieved shortly afterwards. (success = ethical approval) Expected June 2015
Sample Collection: The investigators aim to recruit 150 patients to the study capturing a conservative estimate of 10 per week. All orthopaedic patients will be targeted. The majority are expected to be recruited from the elective theatres. (success = 150 pts recruited) June - September 2015 (onwards)
Metabonomic Analysis Method Development: Establishing Nuclear Magnetic Resonance (NMR) methodology for metabolic profiling of synovial fluid as a sample matrix. Method development of Liquid Chromatography Mass Spectroscopy (LCMS) untargeted and targeted methodology for synovial fluid (success = achieving robust, sensitive methodology) October 2015
Joint Fluid Tribology: Analysis of the lubricating properties of the joint fluid (success = 150 samples assayed) October - December 2015
Metabonomic Analysis: In order to yield the maximum results the investigators aim to analyse using NMR screening with untargeted and targeted LCMS analysis. With approximately 150 patients and thus 450 body fluid samples the investigators are estimating an analysis time of 6 months (success = metabolic profiling and targeted analysis) November - April 2016
Microbial Genetic Analysis: PCR and sequencing of the microbial genetic content of the joint fluid (success = completion in 150 samples) April - June 2016
Collation of results, Analysis and Reporting: Preparation of results for submission to a journal with an impact factor >10. (success = editorial acceptance of manuscript) July - October 2016
- Conditions
- Osteoarthritis, Septic Arthritis, Rheumatoid Arthritis
- Being tested
- Intra-articular aspiration of Joint, Joint irrigation washout, Total Joint Arthroplasty, Revision Joint Arthroplasty
- Keywords
- Osteoarthritis, Septic Arthritis
- Medical subject headings
- Osteoarthritis, Arthritis, Infectious, Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra-articular aspiration of JointProcedure or surgery
Procedural sampling of the joint for diagnostic purposes
Joint irrigation washoutProcedure or surgery
Procedural washout for treatment purposes
Total Joint ArthroplastyProcedure or surgery
Revision Joint ArthroplastyProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Septic Arthritis | Patients suspected of having septic arthritis Receives: Procedure: Intra-articular aspiration of Joint; Procedure: Joint irrigation washout; Procedure: Revision Joint Arthroplasty | |
| Osteoarthritis | Patients suffering with osteoarthritis undergoing an intervention Receives: Procedure: Intra-articular aspiration of Joint; Procedure: Joint irrigation washout; Procedure: Total Joint Arthroplasty; Procedure: Revision Joint Arthroplasty | |
| Joint Revision | Patients who has a prosthetic joint in situ Receives: Procedure: Intra-articular aspiration of Joint; Procedure: Revision Joint Arthroplasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic profiling of all three body fluids in 100 + patients
Measured: 14 months
Secondary outcomes (1)
DNA Profiling of 100 Joint fluid samples for the assay of the microbiome
Measured: 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study startOct 2015
- Primary completionOct 2021 (estimated)
- Study completionOct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chinmay Gupte, MBBChir, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02565160
- Sponsor's protocol ID
- 15/LO/0388
- Status last verified
- Aug 2019
- First submitted
- 28 May 2015
- Last updated
- 20 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Looking for Biomarkers in Human Joint Fluid Using Metabonomic, Microbiomic and Tribological Analysis
- ClinicalTrials.gov ID
- NCT02565160
- Acronym / sponsor ID
- 15/LO/0388
- Conditions
- Osteoarthritis, Septic Arthritis, Rheumatoid Arthritis
- Keywords
- Osteoarthritis, Septic Arthritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Oct 2021 (estimated)
- First posted
- 1 Oct 2015 (estimated)
- 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.
Making the diagnosis underlying a painful, swollen joint currently involves aspiration followed by numerous microbiological and biochemical laboratory tests. This can be costly, time consuming and in the case of an acutely swollen joint, lead to a lengthy inpatient admission. There is an unmet need to provide a quick, easy, reliable dipstick like test to analyse joint fluid in the community, clinic, or emergency department setting.
The investigators aim to use well established metabonomic techniques to:
- Analyse fluid from patients with swollen joints
- Identify potential biomarkers of inflammatory, infective and osteoarthritic causes of joint swelling
- Correlate this with lubrication and wear properties of the fluid The long term goal is to develop time saving, cost effective, non-invasive diagnostic tests to improve management of a swollen joint. The biomedical research centre at Imperial provides a unique and unparalleled clinical and scientific environment to conduct this research. The Imperial College division of Computational and Systems Medicine has an international reputation in metabonomics and this, together with the high volume of patients with swollen joints treated at Imperial National Health Service Trust (c1000/yr) ensures that the study can take place in an environment conductive to success.
Detailed description
Swollen joints represent a diagnostic challenge. Possible diagnoses include: osteoarthritis, gout, rheumatological disease or infection. Diagnostic methods are limited to microscopy, microbiology and trace analysis. These methods can be slow, time consuming, expensive and often inconclusive.
Osteoarthritis varies in the severity of any inflammatory response and subsequent symptoms. To date no molecular link has been established to explain this ambiguity. Previous studies have identified metabolites of the inflammatory response but failed to investigate any correlation with symptoms or response to targeted injections.
Microbial infections of joints are destructive. It typically takes 2-3 days to identify a causative organism and confirm diagnosis. Recent studies suggest low-level bacterial colonisation within joints. The investigators aim to analyse the joint fluid for any bacterial colonisation using enrichment and 16S Polymerase Chain Reaction (PCR) then correlate the results to the metabolic profile. In addition the investigators aim to seek metabolites indicative of the presence of a biofilm which, if present severely limits treatment options.
Metabonomics is the quantitative measurement of the dynamic multiparametric response of a living system to pathophysiological stimuli or genetic modification. This provides a global metabolic profile despite a complex biological sample and has proven useful in many fields.
Our hypotheses are:
- Each pathology will have a unique metabolic profile
- Inflammatory osteoarthritis will contain a different metabolic profile and potentially biomarkers to treatment and/or response
- Specifically the presence and detection of organism sub-type and biofilm biomarkers
- These profiles can be characterised by analysis of blood, urine and joint fluid
- This data can be used to generate diagnostic tests that will aid management of a swollen joint.
- There will be a correlation between metabolic profile and lubricant properties of the joint fluid, that can be utilised in future engineering strategies to manage osteoarthritis.
- To analyse joint fluid from osteoarthritic joints to identify potential biomarkers of the disease and further understanding of the cartilage destruction pathways 2. To assess population variances in joint fluid composition using metabonomics and whether this composition correlates to arthropathy of joints 3. To study the lubrication and wear properties of the joint fluid and understand how the metabolic profile influences lubrication and subsequently joint wear.
- To study joint fluid using metabonomics to identify biomarkers of bacterial colonisation in tandem with microbial 16S Polymerase Chain Reaction and genomic sequencing.
Project Timeline:
Phases of the project are to be as follows:
Full research, Site and Ethical Approval: Provisional ethics is already granted. No obstacles to research and site approval are expected and this should be achieved shortly afterwards. (success = ethical approval) Expected June 2015
Sample Collection: The investigators aim to recruit 150 patients to the study capturing a conservative estimate of 10 per week. All orthopaedic patients will be targeted. The majority are expected to be recruited from the elective theatres. (success = 150 pts recruited) June - September 2015 (onwards)
Metabonomic Analysis Method Development: Establishing Nuclear Magnetic Resonance (NMR) methodology for metabolic profiling of synovial fluid as a sample matrix. Method development of Liquid Chromatography Mass Spectroscopy (LCMS) untargeted and targeted methodology for synovial fluid (success = achieving robust, sensitive methodology) October 2015
Joint Fluid Tribology: Analysis of the lubricating properties of the joint fluid (success = 150 samples assayed) October - December 2015
Metabonomic Analysis: In order to yield the maximum results the investigators aim to analyse using NMR screening with untargeted and targeted LCMS analysis. With approximately 150 patients and thus 450 body fluid samples the investigators are estimating an analysis time of 6 months (success = metabolic profiling and targeted analysis) November - April 2016
Microbial Genetic Analysis: PCR and sequencing of the microbial genetic content of the joint fluid (success = completion in 150 samples) April - June 2016
Collation of results, Analysis and Reporting: Preparation of results for submission to a journal with an impact factor >10. (success = editorial acceptance of manuscript) July - October 2016
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Septic Arthritis | – | Procedure: Intra-articular aspiration of Joint, Procedure: Joint irrigation washout, Procedure: Revision Joint ArthroplastyPatients suspected of having septic arthritis |
| Osteoarthritis | – | Procedure: Intra-articular aspiration of Joint, Procedure: Joint irrigation washout, Procedure: Total Joint Arthroplasty, Procedure: Revision Joint ArthroplastyPatients suffering with osteoarthritis undergoing an intervention |
| Joint Revision | – | Procedure: Intra-articular aspiration of Joint, Procedure: Revision Joint ArthroplastyPatients who has a prosthetic joint in situ |
Who may qualify
- Ages
- 16 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- In summary we expect to recruit 150 subjects and sample three body fluid types. In some cases control and multiple time points will be collected.
Key inclusion criteria (5 listed)
- The patients will be recruited in several scenarios.
Key exclusion criteria (3 listed)
- No patient under 16 years or age or older than 80 years will be entered for the study.
- Any female patient who is pregnant will be excluded.
- Any patient medicated with anti-coagulants will be excluded.
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 |
|---|---|---|
| Intra-articular aspiration of JointProcedural sampling of the joint for diagnostic purposes | Procedure or surgery | Joint Revision, Osteoarthritis, Septic Arthritis |
| Joint irrigation washoutProcedural washout for treatment purposes | Procedure or surgery | Osteoarthritis, Septic Arthritis |
| Total Joint Arthroplasty | Procedure or surgery | Osteoarthritis |
| Revision Joint Arthroplasty | Procedure or surgery | Joint Revision, Osteoarthritis, Septic Arthritis |
Primary outcome
Metabolic profiling of all three body fluids in 100 + patients
Time frame: 14 months
1 secondary outcome
DNA Profiling of 100 Joint fluid samples for the assay of the microbiome
Time frame: 14 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Individual participant dataSharing planned: No
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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.
Chinmay Gupte, MBBChir principal investigator
Imperial College London
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 Osteoarthritis and Septic Arthritis, run by Imperial College London at 1 site in United Kingdom.
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 5 inclusion and 3 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 20 Aug 2019. 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 United Kingdom. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic profiling of all three body fluids in 100 + patients (time frame: 14 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Aug 2019.