An observational study in Inflammation, sponsored by University Hospital, Geneva. Status unknown at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-03-04.
Sponsored by University Hospital, Geneva · Observational
Cytochromes P450, main enzymes of drug metabolism, play a prominent role in the first-pass metabolism of oral substances. Inter-individual variability in their activity due to genetic and environmental factors has been observed and may be associated with adverse therapeutic outcomes (ineffectiveness or toxicity). The inflammation, whether acute or chronic, can theoretically modulate the pharmacokinetics of drugs by modulating enzyme activity. Indeed, in vitro data and animal models, as well as more limited data in humans, indicate a down-regulation of CYP in the context of inflammation.
The cocktail approach developed and validated in Geneva ("cocktail Geneva") measures the activity of several CYP simultaneously using micro-doses of probe drugs and facilitating sampling (10uL capillary blood) on a dried blood spot.
We intend to measure the activity of CYP in an acute inflammation model (hip surgery and SARS-CoV-2 infection) and chronic inflammation (rheumatoid arthritis, RA). The effect of the biological agent tocilizumab (anti IL-6 receptor) in a treated patient subgroup (patients treated regardless of our study) will be measured after 3 months of treatment.
The main objective is to determine if interleukin 6 levels are correlated with the activity of CYP450 in patients with acute (orthopedic surgery - hip or SARS-CoV-2 infection) or chronic inflammation (RA).
Secondary objectives are:
3,536 studies on the registry are indexed under Inflammation; 642 are open to participants now.
This study's planned enrollment of 106 is close to the median of 100 across 864 observational studies indexed under Inflammation.
Browse Inflammation studies →University Hospital, Geneva is the lead sponsor of 379 studies on the registry; 70 are open to participants now.
Compared within Inflammation, the registry's first condition term, which may not be this study's main condition. Counted across the registry records on this site, refreshed daily. How we classify →
Patients included in the study will be patients with either chronic inflammation (patients with rheumatoid arthritis) or with acute inflammation (patients undergoing hip surgery or with COVID-19). All patients will be recruited at the Geneva University Hospitals.
--> Inclusion Criteria: For hip surgery and chronic inflammation groups
For SARS-CoV-2 infection group
Understanding of French language and ability to give a written inform consent
--> Exclusion Criteria: For hip surgery and chronic inflammation groups
For SARS-CoV-2 infection group
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
patients undergoing hip surgery
Diagnostic Test: CYP phenotyping
patients with rheumatoid arthritis
Diagnostic Test: CYP phenotyping
patients with SARS-CoV-2 infection
Diagnostic Test: CYP phenotyping
Phenotyping using a simplified version of the Geneva cocktail
Evaluate the impact of IL6 levels on the activity of CYPs in patients with acute (post orthopaedic surgery -hip or post SARS-CoV-2 infection) and chronic (rheumatoid arthritis) inflammation.
The phenotyping probe drugs used in this study will be given as 2 capsules: one capsule of Omeprazole 10 mg and one capsule containing the remaining probe 'cocktail' drugs (caffeine 50 mg, flurbiprofen 10 mg, dextromethorphan 10 mg, midazolam 1 mg, bupropion 20 mg). The enzymatic activities of the following CYP will be assessed by specific metabolite/probe single point concentration ratios (metabolic ratios-MR) in capillary blood: * CYP1A2 * CYP2B6 * CYP2C9 * CYP2C19 * CYP2D6 * CYP3A4
Time frame: 1 week
Evaluate the correlation between the activity of CYPs and CRP levels
The routine concentration of the inflammatory marker C-reactive protein (CRP) will be measured in blood
Time frame: 1 week or 3 months
Evaluate the correlation between the activity of CYPs and TNF-α levels
TNF-α blood concentrations will be measured by using the Fluorokine MAP Cytokine Multiplex Elisa.
Time frame: 1 week or 3 months
Evaluate the correlation between the activity of CYPs and IL-1β levels
IL-1β blood concentrations will be measured by using the Fluorokine MAP Cytokine Multiplex Elisa.
Time frame: 1 week
Evaluate the correlation between the activity of CYPs and IFN-γ levels
IFN-γ blood concentrations will be measured by using the Fluorokine MAP Cytokine Multiplex Elisa.
Time frame: 1 week
Assess if tocilizumab reverse the activity of CYP in patients with RA after 3 months of treatment
Comparison of CYP function before and 3 months after the beginning of the Tocilizumab treatment.
Time frame: 3 months
Assess if SARS-CoV-2 infection modify pharmacokinetic parameters of concomitant medications which are CYPs substrates
Comparison of plasma concentrations of CYPs substrates, when COVID-19 patients received any CYPs substrates
Time frame: 3 months
Evaluate the correlation between inflammatory markers, CYP function and intensity of fatigue (MFI) and pain (NRS)
Function and intensity of fatigue will be measured with the validated French version of the Multidimensional Fatigue Inventory; pain will be measured with the numeric rating scale (NRS) 0 to 10 (0 = no pain and 10 = worst pain imaginable).
Time frame: 1 week
This study is status unknown, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.
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