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Evaluation of CYP450 Activities in Diabetic Patients vs. Non-diabetic Subjects

NCT02291666 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 73

Last updated 2019-07-23

No results posted yet for this study

Summary

Type 2 diabetes (T2D) could modulate CYP450 activities involved in drug-metabolism and cardiovascular homeostasis. We propose to carry out, for the first time, a comprehensive characterization of the effects of T2D on the expression and activity of major CYP450s. In our studies, patients with T2D will be studied since hyperglycaemia and/or hyperinsulinemia are believed to modulate CYP450s. This vicious cycle puts patients at risk of micro- and macro-vascular complications and inadequately controlled T2D due to high intersubject variability in drug disposition and action.

Characterization of the effects of T2D on drug metabolism capacity will be performed using a cocktail of CYP450 probe drugs.

CYP450 phenotype will be determined in 3 groups of patients (n=126 patients): 1) 42 T2D patients with good glycemic control; 2) 42 T2D patients with poor glycemic control; and 3) 42 non-T2D healthy subjects following a single oral administration of a cocktail of CYP450 probe drugs. Subjects will receive the CRCHUM-MT cocktail consisting of caffeine (CYP1A2), bupropion (CYP2B6), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A4/5) and chlorxozaxone (which will be administered separately) (CYP2E1). Serial blood samples will be drawn and urine collected. Metabolic ratios will be calculated and compared between three groups of subjects. Other co-variables to be studied include T2D biomarkers at baseline (glucose, insulin, HbA1c), medications, genetic polymorphisms and inflammatory markers.

Our cocktail probe drug approach should allow us to demonstrate the effects of T2D on the activity of major CYP450s. Moreover, this project will indicate to us whether glycemic control should be considered as a covariate of intersubject variability in drug metabolism capacity.

Conditions

Interventions

DRUG

CRCHUM-MT cocktail

Sponsors & Collaborators

  • Canadian Institutes of Health Research (CIHR)

    collaborator OTHER_GOV

  • Centre hospitalier de l'Université de Montréal (CHUM)

    lead OTHER

Principal Investigators

  • Veronique Michaud, BPharm, PhD · Centre de recherche du Centre Hospitalier de l'université de Montréal (CHUM)

  • Jean-Louis Chiasson, MD · Centre hospitalier de l'Université de Montréal (CHUM)

Study Design

Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2015-04-30
Primary Completion
2019-07-31
Completion
2019-07-31

Countries

  • Canada

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02291666 on ClinicalTrials.gov