InflammationNCT03262051
Impact of Acute and Chronic Inflammation on Cytochromes P450 Activity Measured With Dried Blood Spot
An observational study of Inflammation, run by University Hospital, Geneva at 1 site in Switzerland.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammation
- What is being tested?
- CYP phenotyping
- How many people
- 106 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Sep 2017to 1 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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
- Male and female patients diagnosed with rheumatoid arthritis or undergoing an elective hip surgery
- Age > 18 years old
- Understanding of French language and ability to give a written inform consent
For SARS-CoV-2 infection group
- Male and female patients diagnosed with SARS-CoV-2 infection (positive RT-PCR) and CRP > 30 mg/L
- Age > 18 years old
- Understanding of French language and ability to give a written inform consent --> Exclusion Criteria: For hip surgery and chronic inflammation groups
- Pregnant or lactating females
- Severe cardiac failure, severe edema or ascites
- Severe COPD or pulmonary embolism requiring oxygen
- Uncontrolled infection
- Active cancer
- HIV infection
- Renal impairment (defined as serum creatinine concentrations > 1.5 x ULN)
- Hepatic impairment (alteration of hepatic tests AST, ALT, bilirubin, GGT >2 x ULN)
- Inability to give blood samples
- Sensitivity to any of the drugs used
- Intake of drugs altering CYPs activity (based on [1]) except for tocilizumab
For SARS-CoV-2 infection group
- Pregnant or lactating females
- Hospitalized in intensive care unit at time of inclusion
- Hospitalized in intermediate care unit at time of inclusion
- Active cancer
- HIV infection
- Renal impairment (glomerular filtration rate < 30 mL/min/1.73m2)
- Hepatic impairment (Child-Pugh score B and C)
- Inability to give blood samples
- Sensitivity to any of the drugs used
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Geneva University Hospitals, HUG
Geneva
Caroline Samer
About this study
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.
Read more
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:
- To correlate CYPs activities with the levels of other inflammatory markers (CRP, TNF-α, IL-1β, IFN-γ);
- To assess correlation between markers of inflammation, CYP activities and the intensity of fatigue and pain;
- To assess if tocilizumab reverse CYP activity in patients with RA after 3 months treatment;
- To assess if SARS-CoV-2 infection modify pharmacokinetic parameters of concomitant medications which are CYPs substrates
- Conditions
- Inflammation
- Being tested
- CYP phenotyping
- Keywords
- cytochromes P450, chronic inflammation, genotyping, phenotyping, acute inflammation, rheumatoid arthritis, surgery, COVID-19, SARS-CoV-2 infection
- Medical subject headings
- Inflammation, Arthritis, Rheumatoid, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYP phenotypingDiagnostic test
Phenotyping using a simplified version of the Geneva cocktail
| Study group | Role | What they receive |
|---|---|---|
| Patient with acute inflammation (surgery) | patients undergoing hip surgery Receives: Diagnostic Test: CYP phenotyping | |
| Patient with chronic inflammation | patients with rheumatoid arthritis Receives: Diagnostic Test: CYP phenotyping | |
| Patient with acute inflammation (SARS-CoV-2 infection) | patients with SARS-CoV-2 infection Receives: Diagnostic Test: CYP phenotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 week
Secondary outcomes (7)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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).
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start1 Sep 2017
- Primary completion1 Sep 2021 (estimated)
- Study completion1 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Caroline Samer, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03262051
- Sponsor's protocol ID
- 2016-02232
- Other IDs
- 2016
- Status last verified
- Mar 2021
- First submitted
- 21 Aug 2017
- Last updated
- 4 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Acute and Chronic Inflammation on Cytochromes P450 Activity Measured With Dried Blood Spot
- ClinicalTrials.gov ID
- NCT03262051
- Acronym / sponsor ID
- 2016-02232
- Conditions
- Inflammation
- Keywords
- cytochromes P450, chronic inflammation, genotyping, phenotyping, acute inflammation, rheumatoid arthritis, surgery, COVID-19
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 1 Sep 2021 (estimated)
- First posted
- 25 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To correlate CYPs activities with the levels of other inflammatory markers (CRP, TNF-α, IL-1β, IFN-γ);
- To assess correlation between markers of inflammation, CYP activities and the intensity of fatigue and pain;
- To assess if tocilizumab reverse CYP activity in patients with RA after 3 months treatment;
- To assess if SARS-CoV-2 infection modify pharmacokinetic parameters of concomitant medications which are CYPs substrates
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patient with acute inflammation (surgery) | – | Diagnostic Test: CYP phenotypingpatients undergoing hip surgery |
| Patient with chronic inflammation | – | Diagnostic Test: CYP phenotypingpatients with rheumatoid arthritis |
| Patient with acute inflammation (SARS-CoV-2 infection) | – | Diagnostic Test: CYP phenotypingpatients with SARS-CoV-2 infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYP phenotypingPhenotyping using a simplified version of the Geneva cocktail | Diagnostic test | Patient with acute inflammation (SARS-CoV-2 infection), Patient with acute inflammation (surgery), Patient with chronic inflammation |
Primary outcome
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.
Time frame: 1 week
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
7 secondary outcomes
Evaluate the correlation between the activity of CYPs and CRP levels
Time frame: 1 week or 3 months
Evaluate the correlation between the activity of CYPs and TNF-α levels
Time frame: 1 week or 3 months
Evaluate the correlation between the activity of CYPs and IL-1β levels
Time frame: 1 week
Evaluate the correlation between the activity of CYPs and IFN-γ levels
Time frame: 1 week
Assess if tocilizumab reverse the activity of CYP in patients with RA after 3 months of treatment
Time frame: 3 months
Assess if SARS-CoV-2 infection modify pharmacokinetic parameters of concomitant medications which are CYPs substrates
Time frame: 3 months
Evaluate the correlation between inflammatory markers, CYP function and intensity of fatigue (MFI) and pain (NRS)
Time frame: 1 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammation, run by University Hospital, Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Caroline Samer, MD (+41 22 382 99 47, caroline.samer@hcuge.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2021.