Knee OsteoarthritisNCT05225480
Reinforcement of Placebo Response in Knee Osteoarthritis: A Randomised Trial
A study testing Illness perception conversation and research motivation conversation in people with Knee Osteoarthritis, run by Frederiksberg University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Illness perception conversation and research motivation conversation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteDenmark
- Study dates
- 21 Apr 2022to 23 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
The Parker Institute, Bispebjerg-Frederiksberg Hospital
Frederiksberg, Danmark, 2000
About this study
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.
Read the 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.
- Conditions
- Knee Osteoarthritis
- Being tested
- Illness perception conversation, research motivation conversation
- Keywords
- Illness perception, Knee osteoarthritis, Placebo, Randomized trial
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Illness perception conversationBehavioural
A conversation based on the indvidual's knee pain related illness perceptions
research motivation conversationBehavioural
A conversation based on the indvidual's motivation for participating in research
| Study group | Role | What they receive |
|---|---|---|
| intervention arm | Experimental | 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. Receives: Behavioral: Illness perception conversation |
| control arm | Active comparator | 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. Receives: Behavioral: research motivation conversation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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".
Measured: Week two, change from baseline
Secondary outcomes (10)
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.
Measured: Week 0, Change from week -1
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.
Measured: Week two, change from baseline
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).
Measured: Week two, change from baseline
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.
Measured: Week two, end of trial, change from baseline
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).
Measured: Week two, change from baseline
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.
Measured: Week two, change from baseline
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.
Measured: Week 0, change from week -1
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)
Measured: Week two, change from baseline
Doppler activity score
Via ultrasound, the Doppler activity will be measured on a semi-quantitative score from 0-3.
Measured: Week two, change from baseline
Self-reported paracetamol and ibuprofen use for knee pain
Participants will register their daily use of paracetamol and ibuprofen for knee pain
Measured: Week two, change from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start21 Apr 2022
- Primary completion23 Feb 2023
- Study completion23 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized single blind controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Frederiksberg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Psychology and Behavioural Sciences, Aarhus University
- Responsible party
- Principal investigator, Marius Henriksen, Frederiksberg University Hospital
- Investigators
- Marius Henriksen, Professor, Principal investigator, the Parker Institute, Bisbebjerg and Frederiksberg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05225480
- Sponsor's protocol ID
- APPI2-OA-2022-01
- Status last verified
- May 2023
- First submitted
- 13 Jan 2022
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ginnerup-Nielsen E, Jorgensen TS, Dew-Hattens C, Christensen R, Berg JI, Vase L, Dossing A, Nielsen SM, Kristensen LE, Bliddal H, Ellegaard K, Henriksen M. The impact of an illness perception conversation on open-label placebo response in knee osteoarthritis: A randomised controlled trial. Osteoarthritis Cartilage. 2024 Dec;32(12):1610-1619. doi: 10.1016/j.joca.2024.07.005. Epub 2024 Jul 17.
PubMed 39029733
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reinforcement of Placebo Response in Knee Osteoarthritis: A Randomised Trial
- ClinicalTrials.gov ID
- NCT05225480
- Acronym / sponsor ID
- APPI2-OA-2022-01
- Conditions
- Knee Osteoarthritis
- Keywords
- Illness perception, Knee osteoarthritis, Placebo, Randomized trial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Frederiksberg University HospitalUniversity, hospital or other
- Collaborators
- Department of Psychology and Behavioural Sciences, Aarhus University
- Study start
- 21 Apr 2022 (actual)
- Primary completion
- 23 Feb 2023 (actual)
- Study completion
- 23 Feb 2023 (actual)
- First posted
- 4 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized single blind controlled trial
| Arm | Type | Receives |
|---|---|---|
| intervention arm | Experimental | Behavioral: Illness perception conversationThe 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. |
| control arm | Active comparator | Behavioral: research motivation conversationThe 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Illness perception conversationA conversation based on the indvidual's knee pain related illness perceptions | Behavioural | intervention arm |
| research motivation conversationA conversation based on the indvidual's motivation for participating in research | Behavioural | control arm |
Primary outcome
VAS knee pain
Time frame: Week two, change from baseline
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".
10 secondary outcomes
The effect of knee pain variability (VAS) prior to the intervention
Time frame: Week 0, Change from week -1
Brief Illness perception questionnaire
Time frame: Week two, change from baseline
Knee injury and Osteoarthritis Outcome Score
Time frame: Week two, change from baseline
The 30 seconds sit to stand test
Time frame: Week two, end of trial, change from baseline
4x10 meter fast walk test
Time frame: Week two, change from baseline
Stair climbing test
Time frame: Week two, change from baseline
Expectations for Treatment Scale (ETS)
Time frame: Week 0, change from week -1
Synovial hypertrophy score
Time frame: Week two, change from baseline
Doppler activity score
Time frame: Week two, change from baseline
Self-reported paracetamol and ibuprofen use for knee pain
Time frame: Week two, change from baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
- Derived from this study: PubMed 39029733Ginnerup-Nielsen E, Jorgensen TS, Dew-Hattens C, Christensen R, Berg JI, Vase L, Dossing A, Nielsen SM, Kristensen LE, Bliddal H, Ellegaard K, Henriksen M. The impact of an illness perception conversation on open-label placebo response in knee osteoarthritis: A randomised controlled trial. Osteoarthritis Cartilage. 2024 Dec;32(12):1610-1619. doi: 10.1016/j.joca.2024.07.005. Epub 2024 Jul 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marius Henriksen, Professor principal investigator
the Parker Institute, Bisbebjerg and Frederiksberg Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Illness perception conversation and research motivation conversation in people with Knee Osteoarthritis, run by Frederiksberg University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VAS knee pain (time frame: Week two, change from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05225480, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2023.