Clinical trial NCT05920148: The Immu-KNEE-ty Study
Official title: The Effect of Total Knee Replacement Surgery on Immune Functioning in Elderly
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Immunosenescence
Aging
Keywords: Knee arthroplasty
Elderly
Immune functioning
Monocytes
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: Wageningen University and Research
name: Gelderse Vallei Hospital
First posted: 2023-06-27
Enrollment: 14
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Monocyte-derived TNFa production
timeFrame: Change from baseline at 1 week after surgery
Secondary outcomes:
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at 1 day after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at 1 week after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at 1 day after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at 1 week after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: Monocyte-derived cytokine production
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: PBMC (peripheral blood mononuclear cell)-derived cytokine production
timeFrame: Change from baseline at 1 day after surgery
measure: PBMC-derived cytokine production
timeFrame: Change from baseline at 1 week after surgery
measure: PBMC-derived cytokine production
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: PBMC-derived cytokine production
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: Composition of immune cell populations
timeFrame: Change from baseline at 1 day after surgery
measure: Composition of immune cell populations
timeFrame: Change from baseline at 1 week after surgery
measure: Composition of immune cell populations
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: Composition of immune cell populations
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: Systemic inflammation
timeFrame: Change from baseline at 1 day after surgery
measure: Systemic inflammation
timeFrame: Change from baseline at 1 week after surgery
measure: Systemic inflammation
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: Systemic inflammation
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: Phagocytic function of monocytes
timeFrame: Change from baseline at 1 day after surgery
measure: Phagocytic function of monocytes
timeFrame: Change from baseline at 1 week after surgery
measure: Phagocytic function of monocytes
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: Phagocytic function of monocytes
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: Monocyte HLA-DR expression
timeFrame: Change from baseline at 1 day after surgery
measure: Monocyte HLA-DR expression
timeFrame: Change from baseline at 1 week after surgery
measure: Monocyte HLA-DR expression
timeFrame: Change from baseline at ± 2 weeks after surgery
measure: Monocyte HLA-DR expression
timeFrame: Change from baseline at ± 6 weeks after surgery
measure: Synovial inflammation
timeFrame: During surgery
measure: Synovial inflammation
timeFrame: During surgery
Other outcomes:
measure: Body Mass Index
timeFrame: Baseline
measure: American Society of Anesthesiologists (ASA) classification
timeFrame: Baseline
measure: Kellgren-Lawrence classification
timeFrame: Baseline
measure: Knee function and pain
timeFrame: Baseline
measure: Physical function
timeFrame: Baseline
measure: Quality of Life (QoL)
timeFrame: Baseline
measure: Pain as measured by the Numeric Pain Rating Scale (NPRS)
timeFrame: Baseline
measure: Mobility
timeFrame: Baseline
measure: Mobility
timeFrame: Baseline
measure: Mobility
timeFrame: Baseline
measure: Duration of surgery
timeFrame: During surgery
measure: Amount of blood loss
timeFrame: During surgery
measure: Analgesic therapies
timeFrame: 1 week before surgery
measure: Analgesic therapies
timeFrame: During hospitalization
measure: Analgesic therapies
timeFrame: In the 6 weeks after surgery
measure: Cold and flu-like symptoms
timeFrame: In the 6 weeks after surgery
Locations:
city: Ede
country: Netherlands
facility: Gelderse Vallei Hospital
Study officials:
References: