The primary objective of this study is to determine changes in monocyte-derived TNFa production after total knee replacement surgery in elderly. As secondary objective, additional parameters of immune functioning will be assessed. In addition, the…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
immunosenescentie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the change from baseline in monocyte-derived TNFa
production at 1 week after surgery. TNFa production will be measured after ex
vivo stimulation of whole blood with inflammatory stimuli and normalized for
monocyte count.
Secondary outcome
Secondary study parameters are:
- Change from baseline in monocyte-derived cytokine production at 1 day, 1
week, ± 2 weeks and ± 6 weeks post-surgery.
- Change from baseline in additional parameters of immune functioning at 1 day,
1 week, ± 2 weeks and ± 6 weeks post-surgery. These additional parameters of
immune functioning are:
• Composition of immune cell populations (monocytes, lymphocytes,
neutrophils, eosinophils, basophils)
• Systemic inflammation
• Phagocytic function of monocytes
• Monocyte HLA-DR expression
- Synovial inflammation.
- Other study parameters: sex, age, BMI, ASA classification, Kellgren-Lawrence
classification, Patient Reported Outcome Measures (PROMs), functional outcomes,
amount and period of use of analgesic therapies and presence of cold and
flu-like symptoms.
Background summary
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. Vulnerability to infections is particularly prevalent in elderly
with chronic diseases or elderly that experienced an incident, such as a
fall-related trauma or surgery. Most likely, this is 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.
Study objective
The primary objective of this study is to determine changes in monocyte-derived
TNFa production after total knee replacement surgery in elderly. 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.
Study design
Prospective ex vivo study in which immune functioning of elderly will be
assessed at multiple timepoints before and after total knee replacement 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 be measured in monocytes for which blood samples will be used. Changes in
monocyte responsiveness are considered indicative for changes in immune
functioning.
Study burden and risks
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 by the Trombosedienst. 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
but receive a financial compensation of ¤50,-.
Stippeneng 4
Wageningen 6708 WE
NL
Stippeneng 4
Wageningen 6708 WE
NL
Listed location countries
Age
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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05920148 |
| CCMO | NL84069.091.23 |