Effect of Methylprednisolone on Immune Signaling in Hip-arthroplasty Patients

Study Overview
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Brief Summary
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The study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total hip-arthroplasty (THA) surgery. The investigators examine the effect on immune signaling and recovery after surgery. Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo. The investigators hypothesize that the group receiving Methylprednisolone will experience a positive modulation of the immune response and an enhanced recovery.

Detailed Description
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The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects on postoperative pain, postoperative nausea and vomiting are well-documented. Hip-arthroplasty surgery and the inflammatory stress response in general affect the potential of recovery. The basic physiological mechanisms behind restoration of recovery after surgery are still unresolved. The many different immune cells involved in the complex signal response enables wound healing and recovery, and the individual immune signal pattern might be able to predict recovery. The effects of glucocorticoids on this immune signal pattern is unknown and calls for further investigation. The study is to be considered as exploratory. This study is embedded in a primary study registrated as: NCT02445898 For further details please view the EudraCT registration: EudraCT nr.: 2015-000102-19

Official Title
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Effect of Preoperative Intravenous High Dose Methylprednisolone on Immune Signaling in Patients Scheduled for Total Hip-arthroplasty

Conditions
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Osteoarthrosis

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Isotonic Sodium Chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthrosis Undergoing total unilateral hip-arthroplasty surgery Speak and understand Danish Have given informed content Exclusion Criteria: Revision or bilateral hip-arthroplasty surgery General anaesthesia Allergy or intolerance towards Methylprednisolone Local or systemic infection Permanent systemic treatment with steroids within 30 days peroperatively Insulin-dependent diabetes Atrial fibrillation Neurological disease incl. Parkinsons Daily use of hypnotics or sedatives Alcohol abuse >35 units per week Active treatment of ulcer within 3 months preoperatively Cancer disease Autoimmune disease incl. rheumatoid arthritis Pregnant or breast feeding women Menopause <1 year

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylprednisolone<br>Preoperative single high dose of Solu-Medrol 125 mg iv. | Drug: Methylprednisolone<br>* Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)<br>* Other names: Solu-Medrol;|
| Placebo Comparator: Placebo<br>Preoperative single dose of isotonic Sodium Chloride | Drug: Isotonic Sodium Chloride<br>* Placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of plasma-STAT3 (Signal transducer and activator of transcription) from baseline to 48 hours after surgery |  | 48 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of plasma-STAT3 from baseline to 14 days after surgery |  | 14 days after surgery | 
| Change in concentration of plasma-CREB (Adenosine 3',5'-monophosphate response element-binding protein) from baseline to 14 days after surgery |  | 14 days after surgery | 
| Change in concentration of plasma-NF-kB (Nuclear factor kB) from baseline to 14 days after surgery |  | 14 days after surgery | 
| Change in Surgical Recovery Scale score from baseline to 28 days after surgery |  | 28 days after surgery | 
| Change in modified WOMAC (Western Ontario and McMaster Universities Arthritis Index) score from baseline to 28 days after surgery |  | 28 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoids, Immune Signaling, Recovery, Hip arthroplasty, total