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Reinforcement of Placebo Response in Knee Osteoarthritis: A Randomised Trial

Primary Purpose

Knee Osteoarthritis

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Illness perception conversation

research motivation conversation

About this trial

This is an interventional treatment trial for Knee Osteoarthritis focused on measuring Illness perception, Knee osteoarthritis, Placebo, Randomized trial

Eligibility Criteria

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

Inclusion Criteria:

Age ≥50 years
A clinical diagnosis of tibiofemoral OA in the target knee according to the American College of Rheumatology
Average knee pain in the last week during weight bearing activities of at least 4 on a 0 to 10 points scale (0=no pain; 10=worst possible pain).

Exclusion Criteria:

Not able to speak or understand Danish
Scheduled surgery during study participation
History of target knee surgery within 12 months
History of arthroplasty in the target knee
Injection therapy in either knee within 3 months
Current use of oral glucocorticoids
Current use of synthetic or non-synthetic opioids
Contraindications to intra-articular injections, such as wounds or skin rash over injection site.
Planning to start or discontinue other treatment for knee OA in the study participation period
Inflammatory arthritis, such as rheumatoid arthritis or psoriatic arthritis.
Regional pain syndromes
Generalised pain syndromes such as fibromyalgia
Lumbar or cervical nerve root compression syndromes
Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as large knee joint effusion, uncontrolled diabetes, psychiatric and/or neurological disorders, or opiate dependency

Sites / Locations

The Parker Institute, Bispebjerg-Frederiksberg Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

intervention arm

control arm

Arm Description

The illness perception conversation will be delivered in one session during around 15 minutes. The conversation will be based on responses to the eight item Brief illness perception questionnaire and a rating of the most relevant item made by the patient on the same day. The aim of the conversation will be to get an overview of the patient's illness perceptions concerning their knee OA and what is deemed the most maladaptive perceptions by the participant. Participants will be invited to elaborate on their thoughts concerning these perceptions.Although any maladaptive perceptions will be corrected if natural during the conversation, the conversation will not lead to any active attempts of changing illness perceptions. Rather, the conversation focusses on giving patients time and opportunity to express knee pain related perceptions and worries concerning their knee pain.

The control conversation will be delivered in one session during around 15 minutes. In order to create two similar conversational settings where the only difference is the actual content of the conversations. The conversation will be based on responses to an eight item questionnaire concerning motivation for research participation and - similar to the illnes perception conversation - a rating of the most relevant item made by the patient. The aim of the conversation will be to get an overview of the patient's motivation for research participation and let them elaborate on their thoughts concerning their motivation.

Outcomes

Primary Outcome Measures

VAS knee pain

Knee pain defined as "the average level of pain in your knee today" will be assessed with a 100 mm visual analogue scale (VAS) with anchors 0 = "no pain" and 100 = "Worst imaginable pain".

Secondary Outcome Measures

The effect of knee pain variability (VAS) prior to the intervention

The key secondary objective is to assess if pain variability in the week before treatment is a determinant of the effect of the subsequent treatment.

Brief Illness perception questionnaire

The Brief illness perception questionnaire (BIPQ) is a generic questionnaire developed to measure illness perception in a variety of illnesses. The questionnaire is patient-reported and assesses perceptions on the following five dimensions: Identity, Cause, Timeline, Consequences and Cure-Control. It contains eight numerical rating scales questions (0-10) and a memo field based on the patients' own beliefs about their condition. In some circumstances it may be possible to compute an overall score which represents the degree to which the illness is perceived as threatening or benign. To compute the score, reverse score items 3, 4, and 7 and add these to items 1, 2, 5, 6, and 8. A higher score reflects a more threatening view of the illness.

Knee injury and Osteoarthritis Outcome Score

The Knee injury and Osteoarthritis Outcome Score (KOOS) is used to assess patient-reported knee-related symptoms. The KOOS is a patient-reported outcome measurement instrument developed to assess the patient's opinion about their knee and associated problems.KOOS comprises of 42 items in 5 separately scored subdomains: KOOS Pain (9 items), KOOS Symptoms (7 items), Function in daily living (KOOS Function; 17 items), Function in Sport and Recreation (5 items), and Knee-related Quality of Life (4 items). The previous week is the time period considered when answering the questions, and the questions relate to one knee (the target knee in this trial).

The 30 seconds sit to stand test

The 30 seconds chair stand test (30sCST) is a physical performance test that quantifies how many sit-to-stand movements an individual can perform within 30 seconds. The 30sCST is a measure of balance 500 during functional activities and lower extremity function and strength. It is recommended as a 501 performance-based test to assess physical function in people diagnosed with hip or knee OA. From the sitting position in the middle of seat with feet shoulder width apart, flat on the floor, arms crossed at chest, the participant is asked to stand completely up, then sit completely back down, repeatedly for 30 seconds. The total number of complete chair stands (up and down represents one stand) is counted. There is given only one trial. If a full stand is completed at 30 seconds, then this is counted in the total. The same chair is used at all assessments.

4x10 meter fast walk test

The 4x10 meter fast walk test (40mFWT) is a physical performance test that quantifies short distance walking performance. The 40mFWT is a measure of walking speed over short distances and changing direction during walking. It is recommended as a performance-based test to assess physical function in people diagnosed with hip or knee OA (26). The participant is asked to walk as quickly but as safely as possible to a mark 10 m away, return, and repeat for a total distance of 40 m. Regular walking aid is allowed and recorded. Time of one trial, with turn time excluded, is recorded and expressed as speed m/s by dividing distance (40 m) by time (s).

Stair climbing test

A stair climbing test (SCT) is a physical performance test that quantifies how fast an individual can ascend and descend a flight of stairs in a usual manner. The SCT is a measure of balance during functional activities and lower extremity function and strength. It is recommended as a performance-based test to assess physical function in people diagnosed with hip or knee OA. The participant is asked to ascend and descend a flight of stairs in a usual manner, and at a safe and comfortable pace. Use of any walking aid and handrail is permitted and recorded. Total time to ascend and descend steps for one trial is recorded in seconds. The same flight of stairs is used at all assessments.

Expectations for Treatment Scale (ETS)

The expectation for treatment scale (ETS) is a 5-item questionnaire concerning the patients' expectations of a given treatment. (E.g: 1) "I expect the treatment will help me to cope with my complaints", 2) "I expect the treatment will make my complaints disappear", 3) I expect the treatment will improve my energy", 4) "I expect the treatment will improve my physical performance" and 5) "I expect that after the treatment, my complaints will be considerably better". Each question has four response options on a likert scale: "partially disagree", "partially agree","agree", "definitely agree". We will replace the word "treatment" with "saline injection" and "complaint" with "knee pain". The questionnaire has been translated into Danish for this study.

Synovial hypertrophy score

Via ultrasound, the amount of synovial hypertrophy will be measured in mm in position using specific landmarks. The following positions will be examined: 1) The medial joint space and recess (medial longitudinal scan) 2) The lateral joint space and recess (lateral longitudinal scan)

Doppler activity score

Via ultrasound, the Doppler activity will be measured on a semi-quantitative score from 0-3.

Self-reported paracetamol and ibuprofen use for knee pain

Participants will register their daily use of paracetamol and ibuprofen for knee pain

Full Information

NCT ID

NCT05225480

First Posted

January 13, 2022

Last Updated

May 31, 2023

Sponsor

Frederiksberg University Hospital

Collaborators

Department of Psychology and Behavioural Sciences, Aarhus University

1. Study Identification

Unique Protocol Identification Number

NCT05225480

Brief Title

Reinforcement of Placebo Response in Knee Osteoarthritis: A Randomised Trial

Official Title

Reinforcement of Placebo Response in Knee Osteoarthritis: A Randomised Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

April 21, 2022 (Actual)

Primary Completion Date

February 23, 2023 (Actual)

Study Completion Date

February 23, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Frederiksberg University Hospital

Collaborators

Department of Psychology and Behavioural Sciences, Aarhus University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Saline intra-articular injections used as placebo treatments have been shown to provide pain relief in knee osteoarthritis (OA) It has further been shown that beneficial effects can be induced merely by having a conversation with a health professional. The aim of this study is to determine whether an individual conversation based on the individual's illness perception related to knee OA affects the response to an intra-articular treatment with saline in individuals with knee OA.

Detailed Description

Despite many years of research, there is still considerable uncertainty on what causes placebo effects and how these are mediated. Saline is a pharmacologically inert agent frequently used as placebo comparator in clinical trials of intra-articular (IA) treatments for knee osteoarthritis (OA) and patients often experience a significant pain improvement from this treatment even when it is administered as an open label placebo treatment. It has further been shown that beneficial effects can be induced merely by having a conversation with a health professional and several studies have found the alliance between therapist and patient to have a positive effect on treatment outcome in physical rehabilitation indicating that positive attention by itself leads to beneficial treatment outcomes. Still it is unclear wether the effect of an open label placebo treatment can be influenced by a conversation and if the extent of this infleuence depends on the focus of the conversation. The aim of this study is to determine whether a conversation about the individual's illness perception related to knee OA affects the response to a placebo treatment (saline injection) in individuals with knee OA.

6. Conditions and Keywords

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

Knee Osteoarthritis

Keywords

Illness perception, Knee osteoarthritis, Placebo, Randomized trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

randomized single blind controlled trial

Masking

ParticipantOutcomes Assessor

Masking Description

The participants are masked as to which intervention (conversation) is considered the actual intervention. Therapists doing physical tests are blinded to treatment allocation

Allocation

Randomized

Enrollment

103 (Actual)

8. Arms, Groups, and Interventions

Arm Title

intervention arm

Arm Type

Experimental

Arm Description

Arm Title

control arm

Arm Type

Active Comparator

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Illness perception conversation

Intervention Description

A conversation based on the indvidual's knee pain related illness perceptions

Intervention Type

Behavioral

Intervention Name(s)

research motivation conversation

Intervention Description

A conversation based on the indvidual's motivation for participating in research

Primary Outcome Measure Information:

Title

VAS knee pain

Description

Knee pain defined as "the average level of pain in your knee today" will be assessed with a 100 mm visual analogue scale (VAS) with anchors 0 = "no pain" and 100 = "Worst imaginable pain".

Time Frame

Week two, change from baseline

Secondary Outcome Measure Information:

Title

The effect of knee pain variability (VAS) prior to the intervention

Description

The key secondary objective is to assess if pain variability in the week before treatment is a determinant of the effect of the subsequent treatment.

Time Frame

Week 0, Change from week -1

Title

Brief Illness perception questionnaire

Description

Time Frame

Week two, change from baseline

Title

Knee injury and Osteoarthritis Outcome Score

Description

Time Frame

Week two, change from baseline

Title

The 30 seconds sit to stand test

Description

Time Frame

Week two, end of trial, change from baseline

Title

4x10 meter fast walk test

Description

Time Frame

Week two, change from baseline

Title

Stair climbing test

Description

Time Frame

Week two, change from baseline

Title

Expectations for Treatment Scale (ETS)

Description

Time Frame

Week 0, change from week -1

Title

Synovial hypertrophy score

Description

Time Frame

Week two, change from baseline

Title

Doppler activity score

Description

Via ultrasound, the Doppler activity will be measured on a semi-quantitative score from 0-3.

Time Frame

Week two, change from baseline

Title

Self-reported paracetamol and ibuprofen use for knee pain

Description

Participants will register their daily use of paracetamol and ibuprofen for knee pain

Time Frame

Week two, change from baseline

Other Pre-specified Outcome Measures:

Title

Knee joint effusion

Description

As a safety outcome, the presence of knee joint effusion will be recorded for each knee as a dichotomous score (present/absent) using ultrasound.

Time Frame

Week two, change from baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥50 years A clinical diagnosis of tibiofemoral OA in the target knee according to the American College of Rheumatology Average knee pain in the last week during weight bearing activities of at least 4 on a 0 to 10 points scale (0=no pain; 10=worst possible pain). Exclusion Criteria: Not able to speak or understand Danish Scheduled surgery during study participation History of target knee surgery within 12 months History of arthroplasty in the target knee Injection therapy in either knee within 3 months Current use of oral glucocorticoids Current use of synthetic or non-synthetic opioids Contraindications to intra-articular injections, such as wounds or skin rash over injection site. Planning to start or discontinue other treatment for knee OA in the study participation period Inflammatory arthritis, such as rheumatoid arthritis or psoriatic arthritis. Regional pain syndromes Generalised pain syndromes such as fibromyalgia Lumbar or cervical nerve root compression syndromes Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as large knee joint effusion, uncontrolled diabetes, psychiatric and/or neurological disorders, or opiate dependency

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marius Henriksen, Professor

Organizational Affiliation

the Parker Institute, Bisbebjerg and Frederiksberg Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Parker Institute, Bispebjerg-Frederiksberg Hospital

City

Frederiksberg

State/Province

Danmark

ZIP/Postal Code

2000

Country

Denmark

12. IPD Sharing Statement

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Reinforcement of Placebo Response in Knee Osteoarthritis: A Randomised Trial

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