Understanding Pain Mechanisms in Knee Osteoarthritis

NCT ID: NCT05561010

Last Updated: 2022-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-31

Study Completion Date

2023-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Osteoarthritis, Knee Chronic Pain

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Knee osteoarthritis Chronic pain

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Intra-articular injection of bupivacaine

5 ml of bupivacaine (0.25% w/v)

Group Type EXPERIMENTAL

Intra-articular injection of bupivacaine in the knee joint

Intervention Type DRUG

25 participants will be allocated to the bupivacaine arm.

Intra-articular injection of sodium chloride

5 ml of sodium chloride (9mg/ml, 0.9% solution for injection)

Group Type PLACEBO_COMPARATOR

Intra-articular injection of placebo in the knee joint

Intervention Type DRUG

25 participants will be allocated to the placebo arm.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Intra-articular injection of bupivacaine in the knee joint

25 participants will be allocated to the bupivacaine arm.

Intervention Type DRUG

Intra-articular injection of placebo in the knee joint

25 participants will be allocated to the placebo arm.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Bupivacaine hydrochloride Sodium chloride

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Nottingham

OTHER

Sponsor Role collaborator

Versus Arthritis

OTHER

Sponsor Role collaborator

Aalborg University

OTHER

Sponsor Role collaborator

Nottingham University Hospitals NHS Trust

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Professor Brigitte Scammell

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Dr Yasmine Zedan

Role: CONTACT

Phone: 01157484389

Email: [email protected]

References

Explore related publications, articles, or registry entries linked to this study.

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

Reference Type BACKGROUND
PMID: 31034380 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8782136 (View on PubMed)

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. doi: 10.1136/ard.61.5.422.

Reference Type BACKGROUND
PMID: 11959766 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25545011 (View on PubMed)

Bird 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.

Reference Type BACKGROUND
PMID: 11719742 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22796624 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29920331 (View on PubMed)

Zedan 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.

Reference Type DERIVED
PMID: 37433734 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

19OR016

Identifier Type: -

Identifier Source: org_study_id