ImmunosenescenceNCT05920148
The Immu-KNEE-ty Study
An observational study of Immunosenescence and Aging, run by Wageningen University at 1 site in Netherlands.
Trial summary
The goal of this observational study is to determine changes in immune functioning after total knee replacement surgery in elderly. The study population consists of 14 patients aged 65 years or over undergoing primary total knee replacement surgery. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Immunosenescence, Aging
- What is being tested?
- Knee arthroplasty
- Type of treatment
- Surgery or procedure
- How many people
- 14 participants
- Where
- 1 siteNetherlands
- Study dates
- 12 Mar 2024to 11 Dec 2024
- Phase
- Observational
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: The study population consists of 14 patients (classified as ASA II or ASA III) aged 65 years or over, diagnosed with osteoarthritis, undergoing primary total knee replacement surgery.
Who may be able to join
- Planned for primary total knee replacement surgery
- Aged 65 years or over
- Diagnosed with osteoarthritis
- ASA Physical Status Classification of II or III
- Willing to donate a blood sample at 5 different timepoints
- Able to give written informed consent
Who cannot join
- Daily use of high doses NSAIDs within the 14 days before inclusion: Defined as higher than maintenance dose in the "farmacotherapeutisch kompas". For example: acetylsalicylic acid > 4 g/day; diclofenac > 75 mg/day; naproxen > 500 mg/day; ibuprofen> 1600 mg/day; celecoxib > 200 mg/day
- Use of systemic corticosteroids
- Use of antibiotics within the 14 days before inclusion
- Current diagnosis of cancer
- Diagnosed with a primary immunodeficiency disorder (e.g., Severe Combined Immunodeficiency (SCID), Common Variable Immune Deficiency (CVID), X-linked agammaglobulinemia, selective immunoglobulin A deficiency, chronic granulomatous disease)
- Vaccination (e.g., immunization against COVID-19, influenza, pneumonia, and travel-related infections) within the 14 days before inclusion and during the study period
- Current participation in other scientific research
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Total Knee Replacement Surgery on Immune Functioning in Elderly
The goal of this observational study is to determine changes in immune functioning after total knee replacement surgery in elderly. The study population consists of 14 patients aged 65 years or over undergoing primary total knee replacement surgery. Immune functioning will be assessed at multiple timepoints before and after surgery (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery). Each patient will serve as his/her own control. Immune functioning will primarily be assessed by determining the change from baseline in monocyte-derived TNFα production at 1 week after surgery. Changes in monocyte responsiveness are considered indicative for changes in immune functioning. As secondary objective, additional parameters of immune functioning will be assessed. In addition, the course of immune functioning following total knee replacement surgery will be investigated. Burden and potential risks for the patient are estimated to be minor. During the study, 5 blood samples of 20 mL will be collected over a period of ± 12 weeks, resulting in a total blood draw of 100 mL. During surgery a sample of synovial fluid (± 2 mL) will be taken from surgical waste. Before and after surgery patients will report their pain medication intake and the presence of cold and flu-like symptoms in a diary. Patients do not directly benefit from the study.
Read the detailed description
The world population is progressively aging. As humans age, their immune system becomes weaker through a process called immunosenescence. This age-related decline in immune functioning results in an increased susceptibility to infections. Elderly with chronic diseases or elderly who have experienced an incident, such as fall-related trauma or surgery, are particularly vulnerable to these infections, likely due to immunosuppression resulting from such an immune challenge. Currently, there are no standard interventions used to improve immune functioning in these immune-suppressed elderly. However, before the potential of such interventions can be explored, postoperative immune suppression in elderly first needs to be demonstrated.
The goal of this prospective ex vivo study is therefore to determine changes in immune functioning after total knee replacement surgery in elderly.
The study population consists of 14 patients (classified as ASA II or ASA III) aged 65 years or over, diagnosed with osteoarthritis, undergoing primary total knee replacement surgery under general anesthesia.
Immune functioning will be assessed at multiple timepoints before and after surgery (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery). Each patient will serve as his/her own control. Immune functioning will primarily be assessed by determining the change from baseline in monocyte-derived TNFα production at 1 week after surgery. TNFα production will be measured after ex vivo stimulation of whole blood with inflammatory stimuli and normalized for monocyte count. Changes in monocyte responsiveness are considered indicative for changes in immune functioning.
As secondary objective, additional parameters of immune functioning will be assessed. In addition, the course of immune functioning following total knee replacement surgery will be investigated.
Burden and potential risks for the patient are estimated to be minor. During the study, 5 blood samples of 20 mL will be collected over a period of ± 12 weeks, resulting in a total blood draw of 100 mL. Blood sampling will be combined with regular care visits, with the exception of one occasion where blood sampling will be performed at home. Patients could experience mild pain by the venipuncture, which occasionally leads to lightheadedness, fainting and hematoma. During surgery a sample of synovial fluid (± 2 mL) will be taken from surgical waste. Before and after surgery patients will report their pain medication intake and the presence of cold and flu-like symptoms in a diary. Patients do not directly benefit from the study.
- Conditions
- Immunosenescence, Aging
- Being tested
- Knee arthroplasty
- Keywords
- Knee arthroplasty, Elderly, Immune functioning, Monocytes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Knee arthroplastyProcedure or surgery
At multiple timepoints (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery) before and after total knee replacement surgery blood will be collected to assess immune functioning
| Study group | Role | What they receive |
|---|---|---|
| Elderly | Not described Receives: Procedure: Knee arthroplasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monocyte-derived TNFa production
TNFα production after ex vivo stimulation of whole blood with inflammatory stimuli corrected for monocyte count
Measured: Change from baseline at 1 week after surgery
Secondary outcomes (30)
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count
Measured: Change from baseline at 1 day after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count
Measured: Change from baseline at 1 week after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count
Measured: Change from baseline at ± 2 weeks after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count
Measured: Change from baseline at ± 6 weeks after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli
Measured: Change from baseline at 1 day after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli
Measured: Change from baseline at 1 week after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli
Measured: Change from baseline at ± 2 weeks after surgery
Monocyte-derived cytokine production
Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli
Measured: Change from baseline at ± 6 weeks after surgery
PBMC (peripheral blood mononuclear cell)-derived cytokine production
Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli
Measured: Change from baseline at 1 day after surgery
PBMC-derived cytokine production
Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli
Measured: Change from baseline at 1 week after surgery
PBMC-derived cytokine production
Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli
Measured: Change from baseline at ± 2 weeks after surgery
PBMC-derived cytokine production
Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli
Measured: Change from baseline at ± 6 weeks after surgery
Composition of immune cell populations
Composition of immune cell populations (white blood cell count and differential) in whole blood
Measured: Change from baseline at 1 day after surgery
Composition of immune cell populations
Composition of immune cell populations (white blood cell count and differential) in whole blood
Measured: Change from baseline at 1 week after surgery
Composition of immune cell populations
Composition of immune cell populations (white blood cell count and differential) in whole blood
Measured: Change from baseline at ± 2 weeks after surgery
Composition of immune cell populations
Composition of immune cell populations (white blood cell count and differential) in whole blood
Measured: Change from baseline at ± 6 weeks after surgery
Systemic inflammation
Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function
Measured: Change from baseline at 1 day after surgery
Systemic inflammation
Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function
Measured: Change from baseline at 1 week after surgery
Systemic inflammation
Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function
Measured: Change from baseline at ± 2 weeks after surgery
Systemic inflammation
Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function
Measured: Change from baseline at ± 6 weeks after surgery
Phagocytic function of monocytes
Phagocytic function of monocytes as measured by the uptake of fluorescent particles
Measured: Change from baseline at 1 day after surgery
Phagocytic function of monocytes
Phagocytic function of monocytes as measured by the uptake of fluorescent particles
Measured: Change from baseline at 1 week after surgery
Phagocytic function of monocytes
Phagocytic function of monocytes as measured by the uptake of fluorescent particles
Measured: Change from baseline at ± 2 weeks after surgery
Phagocytic function of monocytes
Phagocytic function of monocytes as measured by the uptake of fluorescent particles
Measured: Change from baseline at ± 6 weeks after surgery
Monocyte HLA-DR expression
Monocyte HLA-DR expression as measured with fluorescent antibodies
Measured: Change from baseline at 1 day after surgery
Monocyte HLA-DR expression
Monocyte HLA-DR expression as measured with fluorescent antibodies
Measured: Change from baseline at 1 week after surgery
Monocyte HLA-DR expression
Monocyte HLA-DR expression as measured with fluorescent antibodies
Measured: Change from baseline at ± 2 weeks after surgery
Monocyte HLA-DR expression
Monocyte HLA-DR expression as measured with fluorescent antibodies
Measured: Change from baseline at ± 6 weeks after surgery
Synovial inflammation
Synovial inflammation as scored by the surgeon (yes/no)
Measured: During surgery
Synovial inflammation
Synovial inflammation as measured by cytokine and chemokine levels in synovial fluid
Measured: During surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2023
- Study start12 Mar 2024
- Primary completion11 Dec 2024
- Study completion11 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ImmunosenescenceStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wageningen University
- Sponsor type
- University, hospital or other
- Collaborators
- Wageningen University and Research, Gelderse Vallei Hospital
- Responsible party
- Principal investigator, Klaske van Norren, Wageningen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05920148
- Sponsor's protocol ID
- NL84069.091.23
- Status last verified
- Jun 2024
- First submitted
- 15 Jun 2023
- Last updated
- 4 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Total Knee Replacement Surgery on Immune Functioning in Elderly
- ClinicalTrials.gov ID
- NCT05920148
- Acronym / sponsor ID
- NL84069.091.23
- Conditions
- Immunosenescence, Aging
- Keywords
- Knee arthroplasty, Elderly, Immune functioning, Monocytes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Wageningen UniversityUniversity, hospital or other
- Collaborators
- Wageningen University and Research, Gelderse Vallei Hospital
- Study start
- 12 Mar 2024 (actual)
- Primary completion
- 11 Dec 2024 (actual)
- Study completion
- 11 Dec 2024 (actual)
- First posted
- 27 Jun 2023 (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.
The goal of this observational study is to determine changes in immune functioning after total knee replacement surgery in elderly. The study population consists of 14 patients aged 65 years or over undergoing primary total knee replacement surgery. Immune functioning will be assessed at multiple timepoints before and after surgery (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery). Each patient will serve as his/her own control. Immune functioning will primarily be assessed by determining the change from baseline in monocyte-derived TNFα production at 1 week after surgery. Changes in monocyte responsiveness are considered indicative for changes in immune functioning. As secondary objective, additional parameters of immune functioning will be assessed. In addition, the course of immune functioning following total knee replacement surgery will be investigated. Burden and potential risks for the patient are estimated to be minor. During the study, 5 blood samples of 20 mL will be collected over a period of ± 12 weeks, resulting in a total blood draw of 100 mL. During surgery a sample of synovial fluid (± 2 mL) will be taken from surgical waste. Before and after surgery patients will report their pain medication intake and the presence of cold and flu-like symptoms in a diary. Patients do not directly benefit from the study.
Detailed description
The world population is progressively aging. As humans age, their immune system becomes weaker through a process called immunosenescence. This age-related decline in immune functioning results in an increased susceptibility to infections. Elderly with chronic diseases or elderly who have experienced an incident, such as fall-related trauma or surgery, are particularly vulnerable to these infections, likely due to immunosuppression resulting from such an immune challenge. Currently, there are no standard interventions used to improve immune functioning in these immune-suppressed elderly. However, before the potential of such interventions can be explored, postoperative immune suppression in elderly first needs to be demonstrated.
The goal of this prospective ex vivo study is therefore to determine changes in immune functioning after total knee replacement surgery in elderly.
The study population consists of 14 patients (classified as ASA II or ASA III) aged 65 years or over, diagnosed with osteoarthritis, undergoing primary total knee replacement surgery under general anesthesia.
Immune functioning will be assessed at multiple timepoints before and after surgery (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery). Each patient will serve as his/her own control. Immune functioning will primarily be assessed by determining the change from baseline in monocyte-derived TNFα production at 1 week after surgery. TNFα production will be measured after ex vivo stimulation of whole blood with inflammatory stimuli and normalized for monocyte count. Changes in monocyte responsiveness are considered indicative for changes in immune functioning.
As secondary objective, additional parameters of immune functioning will be assessed. In addition, the course of immune functioning following total knee replacement surgery will be investigated.
Burden and potential risks for the patient are estimated to be minor. During the study, 5 blood samples of 20 mL will be collected over a period of ± 12 weeks, resulting in a total blood draw of 100 mL. Blood sampling will be combined with regular care visits, with the exception of one occasion where blood sampling will be performed at home. Patients could experience mild pain by the venipuncture, which occasionally leads to lightheadedness, fainting and hematoma. During surgery a sample of synovial fluid (± 2 mL) will be taken from surgical waste. Before and after surgery patients will report their pain medication intake and the presence of cold and flu-like symptoms in a diary. Patients do not directly benefit from the study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Elderly | – | Procedure: Knee arthroplasty |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- The study population consists of 14 patients (classified as ASA II or ASA III) aged 65 years or over, diagnosed with osteoarthritis, undergoing primary total knee replacement surgery.
Key inclusion criteria (6 listed)
- Planned for primary total knee replacement surgery
- Aged 65 years or over
- Diagnosed with osteoarthritis
- ASA Physical Status Classification of II or III
- Willing to donate a blood sample at 5 different timepoints
Key exclusion criteria (7 listed)
- Daily use of high doses NSAIDs within the 14 days before inclusion: Defined as higher than maintenance dose in the "farmacotherapeutisch kompas". For example: acetylsalicylic acid > 4 g/day; diclofenac > 75 mg/day; naproxen > 500 mg/day; ibuprofen> 1600 mg/day; celecoxib > 200 mg/day
- Use of systemic corticosteroids
- Use of antibiotics within the 14 days before inclusion
- Current diagnosis of cancer
- Diagnosed with a primary immunodeficiency disorder (e.g., Severe Combined Immunodeficiency (SCID), Common Variable Immune Deficiency (CVID), X-linked agammaglobulinemia, selective immunoglobulin A deficiency, chronic granulomatous disease)
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 |
|---|---|---|
| Knee arthroplastyAt multiple timepoints (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery) before and after total knee replacement surgery blood will be collected to assess immune functioning | Procedure or surgery | Elderly |
Primary outcome
Monocyte-derived TNFa production
Time frame: Change from baseline at 1 week after surgery
TNFα production after ex vivo stimulation of whole blood with inflammatory stimuli corrected for monocyte count
30 secondary outcomes
Monocyte-derived cytokine production
Time frame: Change from baseline at 1 day after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at 1 week after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at ± 2 weeks after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at ± 6 weeks after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at 1 day after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at 1 week after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at ± 2 weeks after surgery
Monocyte-derived cytokine production
Time frame: Change from baseline at ± 6 weeks after surgery
PBMC (peripheral blood mononuclear cell)-derived cytokine production
Time frame: Change from baseline at 1 day after surgery
PBMC-derived cytokine production
Time frame: Change from baseline at 1 week after surgery
PBMC-derived cytokine production
Time frame: Change from baseline at ± 2 weeks after surgery
PBMC-derived cytokine production
Time frame: Change from baseline at ± 6 weeks after surgery
Composition of immune cell populations
Time frame: Change from baseline at 1 day after surgery
Composition of immune cell populations
Time frame: Change from baseline at 1 week after surgery
Composition of immune cell populations
Time frame: Change from baseline at ± 2 weeks after surgery
Composition of immune cell populations
Time frame: Change from baseline at ± 6 weeks after surgery
Systemic inflammation
Time frame: Change from baseline at 1 day after surgery
Systemic inflammation
Time frame: Change from baseline at 1 week after surgery
Systemic inflammation
Time frame: Change from baseline at ± 2 weeks after surgery
Systemic inflammation
Time frame: Change from baseline at ± 6 weeks after surgery
Phagocytic function of monocytes
Time frame: Change from baseline at 1 day after surgery
Phagocytic function of monocytes
Time frame: Change from baseline at 1 week after surgery
Phagocytic function of monocytes
Time frame: Change from baseline at ± 2 weeks after surgery
Phagocytic function of monocytes
Time frame: Change from baseline at ± 6 weeks after surgery
Monocyte HLA-DR expression
Time frame: Change from baseline at 1 day after surgery
Monocyte HLA-DR expression
Time frame: Change from baseline at 1 week after surgery
Monocyte HLA-DR expression
Time frame: Change from baseline at ± 2 weeks after surgery
Monocyte HLA-DR expression
Time frame: Change from baseline at ± 6 weeks after surgery
Synovial inflammation
Time frame: During surgery
Synovial inflammation
Time frame: During surgery
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 4 Mar 2025.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immunosenescence and Aging, run by Wageningen University at 1 site in Netherlands.
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 6 inclusion and 7 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 4 Mar 2025. 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 Netherlands. 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?
Monocyte-derived TNFa production (time frame: Change from baseline at 1 week after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Mar 2025.