Clozapine (Clz), an atypical antipsychotic, is the reference medication for patients with treatment-resistant schizophrenia. Due to the high inter-individual variability of its pharmacokinetics and its narrow therapeutic index, a close therapeutic drug monitoring (TDM) of Clz is highly recommended. Several factors can cause a variation in the pharmacokinetics as age, smoking habits, coffee consumption and drug interaction. Genetic factors related to hepatic expression levels of the cytochrome P450 (CYP), regulate the hepatic clearance of Clz, thereby determine its bioavailability. The CYP1A2 and CYP2C19 isoenzymes are mainly responsible for the metabolism of several drugs including Clz. It has been demonstrated that there is an interethnic variation in the expression and function of these two isoenzymes. This variation is caused by single nucleotide polymorphisms (SNPs) of genes encoding these proteins. While the Influence of the different polymorphisms related to CYP1A2 and CYP2C19 have been established especially in Asian and Caucasian populations, no study has examined the impact of these SNPs in the southern Mediterranean populations. Moreover, the impact of these SNPs is very controversial. The present study aims to investigate in Tunisian schizophrenic patients, the influence of genetic (CYP1A2 and CYP2C19 polymorphisms) and non-genetic factors on Clz pharmacokinetics.

NCT04240496

Conditions

1. CYP1A2 Polymorphism
2. CYP2C19 Polymorphism
3. Clozapine
4. Schizophrenia

Interventions

1. Other: Determination of plasma concentration of clozapine/ Genotyping

MeSH:Schizophrenia

HPO:Schizophrenia

Determination of the correlation between the presence of CYP1A2*1F (rs762551;-163C> A), CYP1A2*1C (rs2069514;-3860 G> A) and CYP 2C19*2 (rs4244285; 681G>A) and the variability of C0/Daily dose.. - Technique: PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism).

The effect of caffeine on appetite and body weight is controversial. Mostly epidemiological studies exist that show either a negative effect (reduction of appetite and body weight) or no effect. In this trial we are going to study the results of the consumption of 5mgr/kgr body weight of caffeine on appetite, food consumption and hormones ghrelin, asprosin, leptin and pancreatic polypeptide in relation to gene polymorphisms that affect caffeine metabolism and body weight. Seventy subjects will participate in a cross sectional study consisting of two trials (with or without the consumption of caffeine) in order to study the aforementioned parameters. Differences of total calories consumption between fast metabolizers of caffeine and the rest of the participants is the primary outcome.

NCT04514588

Conditions

1. Food Consumption and Appetite
2. Food Habits
3. Caffeine

Interventions

1. Dietary Supplement: caffeine consumption

MeSH:Body Weight

Molecular and biochemical parameters that are going to be recorded with the utilization of standardized generally accepted protocols are blood pressure, body weight and other anthropometric parameters, blood levels of ghrelin, asprosin, leptin, pancreatic polypeptide, insulin and glucose, and genetic markers that are related to caffeine metabolism (CYP1A2 rs2069514 και CYP1A2 rs762251), as well as to an obesity genetic risk score (32SNPs).