The Immu-KNEE-ty Study

Aging Clinical Trial

Official title:

The Effect of Total Knee Replacement Surgery on Immune Functioning in Elderly

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05920148
• Other study ID #: NL84069.091.23
• Status: Recruiting
• Start date: March 12, 2024
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: Wageningen University
• Contact: Klaske van Norren, PhD
• Phone: +31 (0)317 48 50 93
• Email: klaske.vannorren[@]wur.nl
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Immunosenescence

Intervention

Procedure:
• Knee arthroplasty
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

Locations

Country	Name	City	State
Netherlands	Gelderse Vallei Hospital	Ede

Sponsors (3)

Lead Sponsor	Collaborator
Wageningen University	Gelderse Vallei Hospital, Wageningen University and Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body Mass Index	Body Mass Index	Baseline
Other	American Society of Anesthesiologists (ASA) classification	ASA classification	Baseline
Other	Kellgren-Lawrence classification	Kellgren-Lawrence classification	Baseline
Other	Knee function and pain	Knee function and pain as measured by the Oxford Knee Score (OKS)	Baseline
Other	Physical function	Physical function as measure by the Knee injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS)	Baseline
Other	Quality of Life (QoL)	QoL as measured by EQ-5D	Baseline
Other	Pain as measured by the Numeric Pain Rating Scale (NPRS)	Pain as measured by the NPRS	Baseline
Other	Mobility	Timed Up and Go (TUG) test	Baseline
Other	Mobility	Sit to Stand (STS) test	Baseline
Other	Mobility	10 Meter Walk Test (10MWT)	Baseline
Other	Duration of surgery	Duration of surgery	During surgery
Other	Amount of blood loss	Amount of blood loss	During surgery
Other	Analgesic therapies	Amount of analgesic therapies recorded in a pain medication diary	1 week before surgery
Other	Analgesic therapies	Amount of analgesic therapies recorded in a pain medication diary	During hospitalization
Other	Analgesic therapies	Amount of analgesic therapies recorded in a pain medication diary	In the 6 weeks after surgery
Other	Cold and flu-like symptoms	Cold and flu-like symptoms in a diary	In the 6 weeks after surgery
Primary	Monocyte-derived TNFa production	TNFa production after ex vivo stimulation of whole blood with inflammatory stimuli corrected for monocyte count	Change from baseline at 1 week after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count	Change from baseline at 1 day after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count	Change from baseline at 1 week after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count	Change from baseline at ± 2 weeks after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count	Change from baseline at ± 6 weeks after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli	Change from baseline at 1 day after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli	Change from baseline at 1 week after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli	Change from baseline at ± 2 weeks after surgery
Secondary	Monocyte-derived cytokine production	Cytokine production after ex vivo stimulation of isolated monocytes with inflammatory stimuli	Change from baseline at ± 6 weeks after surgery
Secondary	PBMC (peripheral blood mononuclear cell)-derived cytokine production	Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli	Change from baseline at 1 day after surgery
Secondary	PBMC-derived cytokine production	Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli	Change from baseline at 1 week after surgery
Secondary	PBMC-derived cytokine production	Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli	Change from baseline at ± 2 weeks after surgery
Secondary	PBMC-derived cytokine production	Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli	Change from baseline at ± 6 weeks after surgery
Secondary	Composition of immune cell populations	Composition of immune cell populations (white blood cell count and differential) in whole blood	Change from baseline at 1 day after surgery
Secondary	Composition of immune cell populations	Composition of immune cell populations (white blood cell count and differential) in whole blood	Change from baseline at 1 week after surgery
Secondary	Composition of immune cell populations	Composition of immune cell populations (white blood cell count and differential) in whole blood	Change from baseline at ± 2 weeks after surgery
Secondary	Composition of immune cell populations	Composition of immune cell populations (white blood cell count and differential) in whole blood	Change from baseline at ± 6 weeks after surgery
Secondary	Systemic inflammation	Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function	Change from baseline at 1 day after surgery
Secondary	Systemic inflammation	Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function	Change from baseline at 1 week after surgery
Secondary	Systemic inflammation	Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function	Change from baseline at ± 2 weeks after surgery
Secondary	Systemic inflammation	Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function	Change from baseline at ± 6 weeks after surgery
Secondary	Phagocytic function of monocytes	Phagocytic function of monocytes as measured by the uptake of fluorescent particles	Change from baseline at 1 day after surgery
Secondary	Phagocytic function of monocytes	Phagocytic function of monocytes as measured by the uptake of fluorescent particles	Change from baseline at 1 week after surgery
Secondary	Phagocytic function of monocytes	Phagocytic function of monocytes as measured by the uptake of fluorescent particles	Change from baseline at ± 2 weeks after surgery
Secondary	Phagocytic function of monocytes	Phagocytic function of monocytes as measured by the uptake of fluorescent particles	Change from baseline at ± 6 weeks after surgery
Secondary	Monocyte HLA-DR expression	Monocyte HLA-DR expression as measured with fluorescent antibodies	Change from baseline at 1 day after surgery
Secondary	Monocyte HLA-DR expression	Monocyte HLA-DR expression as measured with fluorescent antibodies	Change from baseline at 1 week after surgery
Secondary	Monocyte HLA-DR expression	Monocyte HLA-DR expression as measured with fluorescent antibodies	Change from baseline at ± 2 weeks after surgery
Secondary	Monocyte HLA-DR expression	Monocyte HLA-DR expression as measured with fluorescent antibodies	Change from baseline at ± 6 weeks after surgery
Secondary	Synovial inflammation	Synovial inflammation as scored by the surgeon (yes/no)	During surgery
Secondary	Synovial inflammation	Synovial inflammation as measured by cytokine and chemokine levels in synovial fluid	During surgery