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Trial record 65 of 80845 for:    measured

Impact of Acute and Chronic Inflammation on Cytochromes P450 Activity Measured With Dried Blood Spot

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ClinicalTrials.gov Identifier: NCT03262051
Recruitment Status : Unknown
Verified September 2017 by Caroline Samer, University Hospital, Geneva.
Recruitment status was:  Recruiting
First Posted : August 25, 2017
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
Caroline Samer, University Hospital, Geneva

Brief 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). 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 ("Geneva Cocktail") measures the activity of several CYP simultaneously using micro-doses of probe drugs and facilitating sampling (10uL capillary blood) on a dried blood spot.

Investigators intend to measure the activity of CYP in an acute inflammation model (hip surgery) and chronic inflammation model (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 chronic inflammation (RA).

Secondary objectives are:

  • To correlate CYPs activities with the levels of other inflammatory markers (CRP, TNF-α);
  • 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.

Condition or disease Intervention/treatment
Inflammation Diagnostic Test: CYP phenotyping

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Study Type : Observational
Estimated Enrollment : 76 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Acute and Chronic Inflammation on Cytochromes P450 Activity Measured With Dried Blood Spot
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : September 1, 2018
Estimated Study Completion Date : September 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis Rashes

Group/Cohort Intervention/treatment
Patient with acute inflammation
patients undergoing hip surgery
Diagnostic Test: CYP phenotyping
Phenotyping using a simplified version of the Geneva cocktail

Patient with chronic inflammation
patients with rheumatoid arthritis
Diagnostic Test: CYP phenotyping
Phenotyping using a simplified version of the Geneva cocktail




Primary Outcome Measures :
  1. Evaluate the impact of IL-6 levels on the activity of CYPs in patients with acute (post orthopaedic surgery) 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


Secondary Outcome Measures :
  1. Correlate CYP activity with other inflammatory markers. CYP activity will be correlated with the levels of the inflammatory marker C-reactive protein (CRP), as well as with the levels of the cytokine Tumor Necrosis Factor alpha (TNF-a). [ Time Frame: 1 week ]
    The routine concentration of the inflammatory marker C-reactive protein (CRP) will be measured in blood. TNF-a blood concentrations will be measured by using the Fluorokine MAP Cytokine Multiplex Elisa.

  2. Evaluate the modification in CYP function in a subgroup of rheumatoid arthritis patients initiating a treatment with IL-6 receptor inhibitor, Tocilizumab. [ Time Frame: 3 months ]
    Comparison of CYP function before and 3 months after the beginning of the Tocilizumab treatment.

  3. Evaluate the correlation between inflammatory markers, CYP function and intensity of fatigue (MFI), pain (NRS). [ Time Frame: 1 week ]
    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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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). All patients will be recruited at the Geneva University Hospitals.
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Pregnant or/and lactating women
  • 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 >1.5x ULN)
  • Hepatic impairment (alteration of hepatic tests AST, ALT, bilirubin, GGT>2x ULN)
  • Inability to give blood samples
  • Sensitivity to any of the drugs used
  • Intake of drugs altering CYPs activity, except for Tocilizumab

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03262051


Contacts
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Contact: Caroline Samer, MD +41 22 382 99 47 caroline.samer@hcuge.ch

Locations
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Switzerland
Geneva University Hospitals, HUG Recruiting
Genève, Switzerland
Contact: Caroline Samer         
Sponsors and Collaborators
University Hospital, Geneva

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Responsible Party: Caroline Samer, Doctor, University Hospital, Geneva, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT03262051     History of Changes
Other Study ID Numbers: 2016-02232
First Posted: August 25, 2017    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Caroline Samer, University Hospital, Geneva:
cytochrome
chronic inflammation
genotyping
phenotyping
acute inflammation
rheumatoid arthritis
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes