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Understanding Pain Mechanisms in Knee Osteoarthritis (UP-KNEE)

Primary Purpose

Osteoarthritis, Knee, Chronic Pain

Status

Not yet recruiting

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Intra-articular injection of bupivacaine in the knee joint

Intra-articular injection of placebo in the knee joint

About this trial

This is an interventional basic science trial for Osteoarthritis, Knee focused on measuring Knee osteoarthritis, Chronic pain

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intra-articular injection of bupivacaine

Intra-articular injection of sodium chloride

Arm Description

5 ml of bupivacaine (0.25% w/v)

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

Outcomes

Primary Outcome Measures

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)

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)

Secondary Outcome Measures

Quantitative sensory testing (QST)

Correlations between change of pain score and QST findings will be assessed.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT05561010

First Posted

December 15, 2020

Last Updated

September 29, 2022

Sponsor

Nottingham University Hospitals NHS Trust

Collaborators

University of Nottingham, Versus Arthritis, Aalborg University

1. Study Identification

Unique Protocol Identification Number

NCT05561010

Brief Title

Understanding Pain Mechanisms in Knee Osteoarthritis

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2022 (Anticipated)

Primary Completion Date

March 2023 (Anticipated)

Study Completion Date

March 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nottingham University Hospitals NHS Trust

Collaborators

University of Nottingham, Versus Arthritis, Aalborg University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoarthritis, Knee, Chronic Pain

Keywords

Knee osteoarthritis, Chronic pain

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intra-articular injection of bupivacaine

Arm Type

Experimental

Arm Description

5 ml of bupivacaine (0.25% w/v)

Arm Title

Intra-articular injection of sodium chloride

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Intra-articular injection of bupivacaine in the knee joint

Other Intervention Name(s)

Bupivacaine hydrochloride

Intervention Description

25 participants will be allocated to the bupivacaine arm.

Intervention Type

Drug

Intervention Name(s)

Intra-articular injection of placebo in the knee joint

Other Intervention Name(s)

Sodium chloride

Intervention Description

25 participants will be allocated to the placebo arm.

Primary Outcome Measure Information:

Title

The change from baseline in pain score during the six-minute walk test

Description

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)

Time Frame

From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo

Title

The change from baseline in pain score at rest

Description

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)

Time Frame

From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo

Secondary Outcome Measure Information:

Title

Quantitative sensory testing (QST)

Description

Correlations between change of pain score and QST findings will be assessed.

Time Frame

Baseline and within 30 minutes after intra-articular injection with bupivacaine or placebo

Title

Brain functional magnetic resonance imaging (fMRI)

Description

Correlations between the change of pain score and brain network activity using predefined seeds in the pain processing regions will be assessed.

Time Frame

Baseline and 1 hour after intra-articular injection with bupivacaine or placebo

Title

Magnetic Resonance Imaging Knee Osteoarthritis Score (MOAKS)

Description

Correlations between the change of pain score and the level of joint damage quantified by MOAKS will be assessed. Higher MOAKS indicate worse outcome.

Time Frame

Baseline

Title

The number of eligible participants who are recruited and randomised to the study

Description

To assess the feasibility of recruitment, the number of eligible participants who are recruited and randomised to the study will be measured.

Time Frame

Through study completion, an average of 6 months

Title

A study-specific checklist to assess the feasibility of the randomisation process

Description

Evaluation of effective randomisation of participants to the study arms using a study-specific checklist and assessment of the randomisation protocol throughout the study.

Time Frame

Through study completion, an average of 6 months

Title

A study-specific questionnaire to assess the acceptability of the trial methods

Description

A study-specific questionnaire will be administered to participants to assess the acceptability of the study design and research process.

Time Frame

Assessed immediately after the final intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dr Yasmine Zedan

Phone

01157484389

Yasmine.Zedan3@nottingham.ac.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Professor Brigitte Scammell

Organizational Affiliation

University of Nottingham

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31034380

Citation

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

Results Reference

background

PubMed Identifier

8782136

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.

Results Reference

background

PubMed Identifier

11959766

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. doi: 10.1136/ard.61.5.422.

Results Reference

background

PubMed Identifier

25545011

Citation

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.

Results Reference

background

PubMed Identifier

11719742

Citation

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.

Results Reference

background

PubMed Identifier

22796624

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.

Results Reference

background

PubMed Identifier

29920331

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.

Results Reference

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Understanding Pain Mechanisms in Knee Osteoarthritis

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