Effect of Tramadol Versus Morphine on PD1 and PD1-ligand in Patients With Chronic Cancer Pain

Study Overview
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Brief Summary
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this work is looking for comparison between the effect of tramadol versus morphine on PD1 and PD1-ligand in patients with chronic cancer pain

Detailed Description
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The use of opioids is the mainstay in the treatment of many types of chronic pain, including cancer and non-cancer-related pain]. Opioids are known to suppress immune function following both acute and chronic administration; however, they appear to be different according to the schedule of administration as well as the state of the organism. Programmed death-1 (PD-1, also known as CD279) belongs to the CD28 receptor superfamily. It is an inhibitory receptor, and its expression is upregulated on activated leukocytes, resulting in an inhibited immune response. PD-1 interacts with two ligands: programmed death ligand-1 (PD-L1, also referred to as B7-H1) and programmed death ligand-2 (PD-L2, also known as B7-DC). PD-L2 is expressed mainly on activated dendritic cells (DCs) and macrophages, whereas PD-L1 is distributed widely. In addition to immune cells, some subsets of tumor cells also express PD-L1 to escape from immunosurveillance. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress.

Official Title
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Comparison Between the Effect of Tramadol Versus Morphine on PD1 and PD1-ligand in Patients With Chronic Cancer Pain

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Tramadol Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with cancer pain of varying etiology, documented metastatic cancer, currently on step I WHO ladder and whose pain necessitates a shift to step II, those who have never received radiotherapy, chemotherapy, or immunosuppressive drugs, -- and in good general and nutritional condition and without infectious diseases at the time of investigation. Exclusion Criteria: abnormal hepatic, renal, and pulmonary function, gastrointestinal pathology, and those with cerebral metastases and/or psychological disorders, patients with contraindication to morphine or tramadol according to their respective data sheets, and patients who could not complete the diary information correctly.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tramadol group<br>tramadol hydrochloride 100 mg three times daily | Drug: Tramadol Hydrochloride<br>* tramadol hydrochloride 100 mg three times daily , morphine sulphate 30 mg twice daily<br>* Other names: morphine sulphate;|
| Active Comparator: morphine group<br>morphine 30 mg twise times daily | Drug: Tramadol Hydrochloride<br>* tramadol hydrochloride 100 mg three times daily , morphine sulphate 30 mg twice daily<br>* Other names: morphine sulphate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in PD1 and PD1ligand | this is flow cytomertic analyses to the human peripheral blood mononuclear cells (PBMCs) will be separated with a Ficoll-Isopaque density gradient. Flow cytometric analyses will be carried out immediately. | baseline(0), day15 , day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain assessment | patient describ his pain severty from 0= no pain to 10= the most sever pain | baseline(0), day15 ,day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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morphine, tramadol, PD1 and PD1 ligand