Understanding Pain Mechanisms in Knee Osteoarthritis (UP-KNEE)

September 29, 2022 updated by: Nottingham University Hospitals NHS Trust

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intra-articular injection of bupivacaine
5 ml of bupivacaine (0.25% w/v)
Drug: Intra-articular injection of bupivacaine in the knee joint
25 participants will be allocated to the bupivacaine arm.
Other Names:
  • Bupivacaine hydrochloride
Placebo Comparator: Intra-articular injection of sodium chloride
5 ml of sodium chloride (9mg/ml, 0.9% solution for injection)
Drug: Intra-articular injection of placebo in the knee joint
25 participants will be allocated to the placebo arm.
Other Names:
  • Sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo
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)
From baseline to approximately one hour after intra-articular injection with bupivacaine or placebo

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative sensory testing (QST)
Time Frame: Baseline and within 30 minutes after intra-articular injection with bupivacaine or placebo
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
Brain functional magnetic resonance imaging (fMRI)
Time Frame: Baseline and 1 hour after intra-articular injection with bupivacaine or placebo
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
Magnetic Resonance Imaging Knee Osteoarthritis Score (MOAKS)
Time Frame: Baseline
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
The number of eligible participants who are recruited and randomised to the study
Time Frame: Through study completion, an average of 6 months
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
A study-specific checklist to assess the feasibility of the randomisation process
Time Frame: Through study completion, an average of 6 months
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
A study-specific questionnaire to assess the acceptability of the trial methods
Time Frame: Assessed immediately after the final intervention
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nottingham University Hospitals NHS Trust

Collaborators

University of Nottingham
Versus Arthritis
Aalborg University

Investigators

  • Principal Investigator: Professor Brigitte Scammell, University of Nottingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2022

Primary Completion (Anticipated)

March 1, 2023

Study Completion (Anticipated)

March 1, 2023

Study Registration Dates

First Submitted

December 15, 2020

First Submitted That Met QC Criteria

September 29, 2022

First Posted (Actual)

September 30, 2022

Study Record Updates

Last Update Posted (Actual)

September 30, 2022

Last Update Submitted That Met QC Criteria

September 29, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19OR016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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