Osteoarthritis, KneeUP-KNEENCT05561010
Understanding Pain Mechanisms in Knee Osteoarthritis
A study testing Intra-articular injection of bupivacaine in the knee joint in people with Osteoarthritis, Knee and Chronic Pain, run by Nottingham University Hospitals NHS Trust.
Trial summary
UP-KNEE study is a feasibility, double-blind, placebo-controlled randomised parallel study in participants with radiographically defined knee OA, and with self-reported chronic knee pain. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Osteoarthritis, Knee, Chronic Pain
- What is being tested?
- Intra-articular injection of bupivacaine in the knee joint
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Oct 2022to Mar 2023
- Phase
- Interventional
- 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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Radiographically defined OA knee changes (K/L > 2);
- Must have self-reported knee pain (measuring at least 30 mm to 80 mm on a 100 mm VAS for rest, use or night pain);
- Able to give informed consent;
- Aged 45 years and older;
- All genders;
- Able to perform the six-minute walk test.
Who cannot join
- Aged less than 45 years;
- Breastfeeding or pregnancy;
- Not having the capacity to consent;
- Non-English speakers;
- Major medical, neurological and psychiatric co-morbidities;
- Hip OA (ipsilateral or contralateral);
Show all 25Show fewer
- Fibromyalgia;
- Sensory dysfunctional illness;
- Chronic pain conditions other than OA;
- Presence of local or systemic infection or suspicion of infection in the knee joint, overlying soft tissue or elsewhere;
- History of septic arthritis in the knee to be injected;
- Acute haemarthrosis in the joint to be injected;
- Recent trauma within 72 hours;
- Prosthetic joint;
- Presence of broken skin or rash over the area to be injected;
- Severe coagulopathy (can take aspirin or anti-platelets inhibitors such as clopidogrel);
- Any anti-coagulant therapy (e.g. warfarin);
- Severe liver disease or severe kidney disease;
- Known hypersensitivity, allergy or intolerance to local anaesthetic / bupivacaine;
- Recently taken other medicines containing local anaesthetic / bupivacaine within 1 month;
- Surgery planned within 3 months of entry to study;
- Neuropathic pain medications such as opioid analgesics, antiepileptic drugs such as pregabalin / gabapentin, and tricyclic antidepressants such as amitriptyline when taken for neuropathic pain treatment;
- Current or recent intake centrally-active medication (e.g. have recently taken monoamine oxidase inhibitor (MAOI));
- Complete heart block;
- The presence of any contraindication for MRI.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Is There a Difference in the Analgesic Response to Intra-articular Bupivacaine Injection in People With Knee Osteoarthritis Pain With or Without Central Sensitisation?: a Feasibility Randomised Controlled Trial
UP-KNEE study is a feasibility, double-blind, placebo-controlled randomised parallel study in participants with radiographically defined knee OA, and with self-reported chronic knee pain.
Read the detailed description
Osteoarthritis (OA) of the knee joint is a common cause of chronic pain, disability and impaired quality of life. Knee OA affects ~ 1 in 5 adults over 45 years, with many requiring major knee surgery to alleviate pain and restore mobility. However, > 1 in 5 patients will continue to suffer from pain despite surgery. It remains largely unknown who will fail to respond, and why.
Chronic postoperative pain may be linked to a particular type of pain, that is not only driven by the joint damage itself but by changes in the central nervous system (central pain). Several lines of evidence support this idea, but there is a need for a better understanding of the underlying mechanisms as well as a better tool to differentiate between peripherally- and centrally-augmented knee pain in order to identify who will benefit the most from knee surgery.
To this end, the proposed research is a feasibility study aiming to provide proof of concept for a future main trial. The study combines the diagnostic power of non-invasive imaging with experimental approaches to investigate central pain by modelling the peripheral effects of knee surgery. This will provide novel insights into the contribution of peripheral and central pain mechanisms in knee OA which can pave the way for better treatment results.
This study is expected to last for one year. It is funded by Versus Arthritis Pain Centre and forms part of a wider scientific project aiming at increasing knowledge and understanding of OA pain.
- Conditions
- Osteoarthritis, Knee, Chronic Pain
- Being tested
- Intra-articular injection of bupivacaine in the knee joint, Intra-articular injection of placebo in the knee joint
- Keywords
- Knee osteoarthritis, Chronic pain
- Medical subject headings
- Osteoarthritis, Knee, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra-articular injection of bupivacaine in the knee jointDrug
Also called Bupivacaine hydrochloride
25 participants will be allocated to the bupivacaine arm.
Intra-articular injection of placebo in the knee jointDrug
Also called Sodium chloride
25 participants will be allocated to the placebo arm.
| Study group | Role | What they receive |
|---|---|---|
| Intra-articular injection of bupivacaine | Experimental | 5 ml of bupivacaine (0.25% w/v) Receives: Drug: Intra-articular injection of bupivacaine in the knee joint |
| Intra-articular injection of sodium chloride | Placebo comparator | 5 ml of sodium chloride (9mg/ml, 0.9% solution for injection) Receives: Drug: Intra-articular injection of placebo in the knee joint |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change from baseline in pain score during the six-minute walk test
The change from baseline in pain score using the Visual Analogue Scale during the six-minute walk test.
(visual analogue scale ranges from 0-100; 0 meaning no pain and 100 worst imaginable pain)
Measured: From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
The change from baseline in pain score at rest
The change from baseline in pain score using the Visual Analogue Scale at rest. (visual analogue scale ranges from 0-100; 0 meaning no pain and 100 worst imaginable pain)
Measured: From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
Secondary outcomes (6)
Quantitative sensory testing (QST)
Correlations between change of pain score and QST findings will be assessed.
Measured: Baseline and within 30 minutes after intra-articular injection with bupivacaine or placebo
Brain functional magnetic resonance imaging (fMRI)
Correlations between the change of pain score and brain network activity using predefined seeds in the pain processing regions will be assessed.
Measured: Baseline and 1 hour after intra-articular injection with bupivacaine or placebo
Magnetic Resonance Imaging Knee Osteoarthritis Score (MOAKS)
Correlations between the change of pain score and the level of joint damage quantified by MOAKS will be assessed. Higher MOAKS indicate worse outcome.
Measured: Baseline
The number of eligible participants who are recruited and randomised to the study
To assess the feasibility of recruitment, the number of eligible participants who are recruited and randomised to the study will be measured.
Measured: Through study completion, an average of 6 months
A study-specific checklist to assess the feasibility of the randomisation process
Evaluation of effective randomisation of participants to the study arms using a study-specific checklist and assessment of the randomisation protocol throughout the study.
Measured: Through study completion, an average of 6 months
A study-specific questionnaire to assess the acceptability of the trial methods
A study-specific questionnaire will be administered to participants to assess the acceptability of the study design and research process.
Measured: Assessed immediately after the final intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2022
- Study startOct 2022 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionMar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nottingham University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nottingham, Versus Arthritis, Aalborg University
- Responsible party
- Sponsor
- Investigators
- Professor Brigitte Scammell, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05561010
- Sponsor's protocol ID
- 19OR016
- Acronym
- UP-KNEE
- Status last verified
- Sep 2022
- First submitted
- 15 Dec 2020
- Last updated
- 30 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019 Apr 27;393(10182):1745-1759. doi: 10.1016/S0140-6736(19)30417-9.
PubMed 31034380Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic. J Rheumatol. 1996 Jun;23(6):1031-6.
PubMed 8782136Hassan BS, Doherty SA, Mockett S, Doherty M. Effect of pain reduction on postural sway, proprioception, and quadriceps strength in subjects with knee osteoarthritis. Ann Rheum Dis. 2002 May;61(5):422-8. doi: 10.1136/ard.61.5.422.
PubMed 11959766Arendt-Nielsen L, Egsgaard LL, Petersen KK, Eskehave TN, Graven-Nielsen T, Hoeck HC, Simonsen O. A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different disease stages and pain levels. Eur J Pain. 2015 Nov;19(10):1406-17. doi: 10.1002/ejp.651. Epub 2014 Dec 29.
PubMed 25545011Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. Ann Emerg Med. 2001 Dec;38(6):639-43. doi: 10.1067/mem.2001.118012.
PubMed 11719742Suokas AK, Walsh DA, McWilliams DF, Condon L, Moreton B, Wylde V, Arendt-Nielsen L, Zhang W. Quantitative sensory testing in painful osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2012 Oct;20(10):1075-85. doi: 10.1016/j.joca.2012.06.009. Epub 2012 Jul 13.
PubMed 22796624Kurien T, Arendt-Nielsen L, Petersen KK, Graven-Nielsen T, Scammell BE. Preoperative Neuropathic Pain-like Symptoms and Central Pain Mechanisms in Knee Osteoarthritis Predicts Poor Outcome 6 Months After Total Knee Replacement Surgery. J Pain. 2018 Nov;19(11):1329-1341. doi: 10.1016/j.jpain.2018.05.011. Epub 2018 Jun 18.
PubMed 29920331Zedan Y, Knaggs R, Cooper D, Kurien T, Walsh DA, Auer DP, Scammell BE. Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation? Protocol of a feasibility randomised controlled trial. BMJ Open. 2023 Jul 11;13(7):e072138. doi: 10.1136/bmjopen-2023-072138.
PubMed 37433734
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is There a Difference in the Analgesic Response to Intra-articular Bupivacaine Injection in People With Knee Osteoarthritis Pain With or Without Central Sensitisation?: a Feasibility Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT05561010
- Acronym / sponsor ID
- UP-KNEE / 19OR016
- Conditions
- Osteoarthritis, Knee, Chronic Pain
- Keywords
- Knee osteoarthritis, Chronic pain
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Nottingham University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- University of Nottingham, Versus Arthritis, Aalborg University
- Study start
- Oct 2022 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 30 Sep 2022 (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.
UP-KNEE study is a feasibility, double-blind, placebo-controlled randomised parallel study in participants with radiographically defined knee OA, and with self-reported chronic knee pain.
Detailed description
Osteoarthritis (OA) of the knee joint is a common cause of chronic pain, disability and impaired quality of life. Knee OA affects ~ 1 in 5 adults over 45 years, with many requiring major knee surgery to alleviate pain and restore mobility. However, > 1 in 5 patients will continue to suffer from pain despite surgery. It remains largely unknown who will fail to respond, and why.
Chronic postoperative pain may be linked to a particular type of pain, that is not only driven by the joint damage itself but by changes in the central nervous system (central pain). Several lines of evidence support this idea, but there is a need for a better understanding of the underlying mechanisms as well as a better tool to differentiate between peripherally- and centrally-augmented knee pain in order to identify who will benefit the most from knee surgery.
To this end, the proposed research is a feasibility study aiming to provide proof of concept for a future main trial. The study combines the diagnostic power of non-invasive imaging with experimental approaches to investigate central pain by modelling the peripheral effects of knee surgery. This will provide novel insights into the contribution of peripheral and central pain mechanisms in knee OA which can pave the way for better treatment results.
This study is expected to last for one year. It is funded by Versus Arthritis Pain Centre and forms part of a wider scientific project aiming at increasing knowledge and understanding of OA pain.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intra-articular injection of bupivacaine | Experimental | Drug: Intra-articular injection of bupivacaine in the knee joint5 ml of bupivacaine (0.25% w/v) |
| Intra-articular injection of sodium chloride | Placebo comparator | Drug: Intra-articular injection of placebo in the knee joint5 ml of sodium chloride (9mg/ml, 0.9% solution for injection) |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Radiographically defined OA knee changes (K/L > 2);
- Must have self-reported knee pain (measuring at least 30 mm to 80 mm on a 100 mm VAS for rest, use or night pain);
- Able to give informed consent;
- Aged 45 years and older;
- All genders;
Key exclusion criteria (25 listed)
- Aged less than 45 years;
- Breastfeeding or pregnancy;
- Not having the capacity to consent;
- Non-English speakers;
- Major medical, neurological and psychiatric co-morbidities;
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 injection of bupivacaine in the knee jointAlso: Bupivacaine hydrochloride25 participants will be allocated to the bupivacaine arm. | Drug | Intra-articular injection of bupivacaine |
| Intra-articular injection of placebo in the knee jointAlso: Sodium chloride25 participants will be allocated to the placebo arm. | Drug | Intra-articular injection of sodium chloride |
Primary outcome
The change from baseline in pain score during the six-minute walk test
Time frame: From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
The change from baseline in pain score using the Visual Analogue Scale during the six-minute walk test. (visual analogue scale ranges from 0-100; 0 meaning no pain and 100 worst imaginable pain)
The change from baseline in pain score at rest
Time frame: From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
The change from baseline in pain score using the Visual Analogue Scale at rest. (visual analogue scale ranges from 0-100; 0 meaning no pain and 100 worst imaginable pain)
6 secondary outcomes
Quantitative sensory testing (QST)
Time frame: Baseline and within 30 minutes after intra-articular injection with bupivacaine or placebo
Brain functional magnetic resonance imaging (fMRI)
Time frame: Baseline and 1 hour after intra-articular injection with bupivacaine or placebo
Magnetic Resonance Imaging Knee Osteoarthritis Score (MOAKS)
Time frame: Baseline
The number of eligible participants who are recruited and randomised to the study
Time frame: Through study completion, an average of 6 months
A study-specific checklist to assess the feasibility of the randomisation process
Time frame: Through study completion, an average of 6 months
A study-specific questionnaire to assess the acceptability of the trial methods
Time frame: Assessed immediately after the final intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2022.
- Background: PubMed 31034380Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019 Apr 27;393(10182):1745-1759. doi: 10.1016/S0140-6736(19)30417-9.
- Background: PubMed 8782136Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic. J Rheumatol. 1996 Jun;23(6):1031-6.
- Background: PubMed 11959766Hassan BS, Doherty SA, Mockett S, Doherty M. Effect of pain reduction on postural sway, proprioception, and quadriceps strength in subjects with knee osteoarthritis. Ann Rheum Dis. 2002 May;61(5):422-8. doi: 10.1136/ard.61.5.422.
- Background: PubMed 25545011Arendt-Nielsen L, Egsgaard LL, Petersen KK, Eskehave TN, Graven-Nielsen T, Hoeck HC, Simonsen O. A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different disease stages and pain levels. Eur J Pain. 2015 Nov;19(10):1406-17. doi: 10.1002/ejp.651. Epub 2014 Dec 29.
- Background: PubMed 11719742Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. Ann Emerg Med. 2001 Dec;38(6):639-43. doi: 10.1067/mem.2001.118012.
- Background: PubMed 22796624Suokas AK, Walsh DA, McWilliams DF, Condon L, Moreton B, Wylde V, Arendt-Nielsen L, Zhang W. Quantitative sensory testing in painful osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2012 Oct;20(10):1075-85. doi: 10.1016/j.joca.2012.06.009. Epub 2012 Jul 13.
- Background: PubMed 29920331Kurien T, Arendt-Nielsen L, Petersen KK, Graven-Nielsen T, Scammell BE. Preoperative Neuropathic Pain-like Symptoms and Central Pain Mechanisms in Knee Osteoarthritis Predicts Poor Outcome 6 Months After Total Knee Replacement Surgery. J Pain. 2018 Nov;19(11):1329-1341. doi: 10.1016/j.jpain.2018.05.011. Epub 2018 Jun 18.
- Derived from this study: PubMed 37433734Zedan Y, Knaggs R, Cooper D, Kurien T, Walsh DA, Auer DP, Scammell BE. Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation? Protocol of a feasibility randomised controlled trial. BMJ Open. 2023 Jul 11;13(7):e072138. doi: 10.1136/bmjopen-2023-072138.
- 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.
Professor Brigitte Scammell principal investigator
University of Nottingham
Questions about this trial
What is this clinical trial studying?
A study testing Intra-articular injection of bupivacaine in the knee joint in people with Osteoarthritis, Knee and Chronic Pain, run by Nottingham University Hospitals NHS Trust.
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 6 inclusion and 25 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 30 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 Dr Yasmine Zedan (01157484389, Yasmine.Zedan3@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change from baseline in pain score during the six-minute walk test (time frame: From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo). The study lists 2 primary outcomes in all. 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 NCT05561010, which also lists 8 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 30 Sep 2022; AzTrials last refreshed its copy on 6 Nov 2026.