Understanding Pain Mechanisms in Knee Osteoarthritis

Chronic Pain Clinical Trial

— UP-KNEE  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05561010
• Other study ID #: 19OR016
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 2022
• Est. completion date: March 2023

Study information

• Verified date: September 2022
• Source: Nottingham University Hospitals NHS Trust
• Contact: Dr Yasmine Zedan
• Phone: 01157484389
• Email: Yasmine.Zedan3[@]nottingham.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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);

• 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.

Related Conditions & MeSH terms

• Chronic Pain
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Intra-articular injection of bupivacaine in the knee joint
25 participants will be allocated to the bupivacaine arm.
• Intra-articular injection of placebo in the knee joint
25 participants will be allocated to the placebo arm.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Nottingham University Hospitals NHS Trust	Aalborg University, University of Nottingham, Versus Arthritis

References & Publications (7)

Arendt-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. — View Citation

Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. Ann Emerg Med. 2001 Dec;38(6):639-43. — View Citation

Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic. J Rheumatol. 1996 Jun;23(6):1031-6. — View Citation

Hassan 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. — View Citation

Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019 Apr 27;393(10182):1745-1759. doi: 10.1016/S0140-6736(19)30417-9. Review. — View Citation

Kurien 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. — View Citation

Suokas 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
Primary	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)	From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
Secondary	Quantitative sensory testing (QST)	Correlations between change of pain score and QST findings will be assessed.	Baseline and within 30 minutes after intra-articular injection with bupivacaine or placebo
Secondary	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.	Baseline and 1 hour after intra-articular injection with bupivacaine or placebo
Secondary	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.	Baseline
Secondary	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.	Through study completion, an average of 6 months
Secondary	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.	Through study completion, an average of 6 months
Secondary	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.	Assessed immediately after the final intervention