View clinical trials related to Pharmacogenetics.
Filter by:Fentanyl is an opioid drug used as analgesic and anaesthetic also in Neonatal Intensive Care Units (NICU), according to the last national and international recommendations, during invasive life support strategies such as mechanical ventilation. Opioids manifest their sedative effect through activation of μ-opioid receptors, which are abundant both in the central and peripheral nervous system. Comparing fentanyl to morphine we can appreciate a much more powerful effect (75-220 major) with lower doses to obtain similar analgesic effect; these characteristics are due to the high lipophilicity of the molecule which easily crosses the blood-brain barrier (BBB). At the same time, fentanyl shows less adverse effects than morphine such as vomiting, nausea, gastrointestinal constipation, respiratory depression, dependence and tolerance. The drug is extensively metabolized by liver enzymes. In routinary clinical practice it has been observed that large interindividual differences are found in the daily dosages needed to achieve pain control. Literature evidences that pharmacodynamic variation related to genotypes in receptor signalling or pain modulators may play an important role in this variability. Many genes are related to fentanyl pharmacodynamics and pharmacokinetics. Some polymorphism in these genes are already known to correlate with toxicity or efficacy of the drug, also in the paediatric population. More polymorphisms could be involved in abnormal pharmacodynamic or pharmacokinetics of fentanyl, therefore studies are necessary to better explain the possible role of pharmacogenetics in precision medicine especially in a very specific population as newborn.
The research is planned as a prospective nested case-control study. The plan is to recruit about 1,200 consecutive subjects whose pharmacotherapy involves the drug(s) of interest within 4.5 years. The basic cohort - the subjects with the newly indicated indication for use: NOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. The ADRs will be analysed by CR by: age, gender, expectancy, severity, association, type (mechanism of event), and outcome, according to the classification of organ systems as well as association with the phenotype. Criteria for bleeding associated with the use of anticoagulant and antiplatelet therapy have been defined; as well as the myotoxicity and hepatotoxicity associated with statin therapy. Samples will be tested for biochemical, haematological, coagulation standard parameters and pharmacogenetic analyses of relevant genes depending on the used therapy. Pharmacogenetic analysis will be performed to genotype the polymorphisms of relevant pharmacogenes: Biological samples and clinical data will be anonymized plus all records of ADRs and other clinical variables will be protected. Possible drug-drug and drug-drug-gene interactions will be evaluated using the Clinical Decision Support System (CDSS) of Lexicomp, PharmGKB, the Flockhart Table, and other systems including panel consensus methods to determine the likelihood of an ADR being associated with drug interactions, and determine whether drug interactions contributed to the occurrence of ADRs to administered CV pharmacotherapy in subjects with variant pharmacogenes of interest (drug-drug-gene interaction). The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs and are good candidates for inclusion in the clinical diagnostic panel for pre-emptive PGx testing.
This project will generate a prospective cohort of geriatric patients with polypharmacy which will be characterized for vulnerability profiles of adverse drug reactions.
This is a single centre, prospective feasibility study and pilot randomised controlled trial of patients scheduled for elective intermediate or major non-cardiac surgery. The investigators plan to randomise up to 200 patients who meet the inclusion criteria to standard care or to personalised perioperative care based on pharmacogenomic testing for drugs commonly used in anaesthesia and postoperative pain management e.g., opioids - morphine, oxycodone and tramadol; anti-emetics - metoclopramide and ondansetron; and non-steroidal drugs - celecoxib and ibuprofen. The investigators hypothesise that pharmacogenomic testing is feasible prior to elective surgery and through 'personalised prescribing' for precision tailored perioperative care the investigators will improve patient's postoperative quality of recovery, including pain management.
Acetaminophen (APAP) is the most commonly used NSAIDS in clinic, and it is also a common cause of drug-induced liver injury (DILI). In 2012, the proportion of DILI caused by APAP in the United States was 51%, while in Asia, it was only 7.10%. Previously, a small cohort study in the United States screened for some of the susceptibility genes for DILI due to APAP by the Genome wide association study (GWAS) method. However, the genetic susceptibility loci based on the US cohort were not applicable to the Chinese population. Therefore, we make a study design include Chinese population who ingested APAP and divided them into case group and control group according to the occurrence of DILI. We hope to be able to find the root of differences at the genetic level and explore new pathogenic mechanisms.
The purpose of this study is to assess the prevalence of veterans with major depressive disorder (MDD) who are being treated with a medication that has current Clinical Pharmacogenetics Implementation Consortium (CPIC) or Pharmacogenomics Knowledgebase (PharmGKB) actionable recommendations that have a pharmacogenomic variation that impacts the safety or efficacy of the subject medication.
This is a mechanism-based study in healthy adults to determine the effect of the CYP2C9 M1L gene polymorphism on the functional activity of the encoded CYP2C9 enzyme towards the probe substrate naproxen. CYP2C9 activity will be evaluated by measurement of O-desmethyl naproxen and unchanged naproxen in 24-hour urine following administration of a single oral dose of naproxen (Aleve) in Yup'ik Alaska Native adult men and women who were previously determined in a separate observational study to be homozygous for the CYP2C9*1 allele or a carrier of the CYP2C9 M1L allele.
Clozapine is prescribed to patients with psychosis in whom other treatments have not worked. Research has shown, however, that clozapine may be associated with weight gain and abnormal blood sugar levels in some patients. There is strong evidence to suggest that genetic variation between individuals plays an important role in the development of these side effects in response to the medication. Our research aims to evaluate the effects of two genes and the blood level of clozapine on side-effects such as weight changes and blood sugar levels in patients receiving clozapine treatment. From out-patient clinics in Cwm Taf UHB, the investigators aim to recruit 160 patients who are taking clozapine; collect information/ measurements from recruits relating to size/ weight/ BMI, risk of diabetes and blood samples to measure markers of blood sugar, fat/lipids, clozapine and its breakdown products, blood cells and variants of two specific genes. From this information the investigators will be particularly interested to understand if there is any association between the variation in these two genes with weight gain or changes in blood sugar, in patients taking clozapine.
The efficacy and safety of antiretroviral therapy and the damage caused by chronic inflammation in the presence of the virus has recently lead to the consideration of initiating antiretroviral therapy earlier than what is required to prevent opportunistic diseases. Although there may be subtle differences, all recommended antiretroviral combinations for first-line therapy are considered equally effective. Nevertheless, treatment success requires high levels of adherence, which is linked to tolerability and the minimization of adverse effects. The genes coding the enzymes that are involved in the antiretroviral clearance pathways and the transmembrane transport of drugs are known. These genetic variations can determine the interindividual variations in plasma concentration with the same doses. Both pharmacogenomics (PG) and therapeutic drug monitoring (TDM) may contribute to the individualization of therapy in different chronic conditions through dosing optimization and are associated with a lower risk of concentration-dependent toxicity and potentially greater efficacy. The use of these strategies in the context of antiretroviral therapy is in early stage of development. Following, our main hypothesis is that PG + TDM dose adjustment of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection is non-inferior in terms of efficacy, has improved safety, and shows a better cost/effectiveness profile than the standard approach with non adjusted doses. To evaluate our hypothesis we developed this multicenter randomized clinical trial, where patients from 4 clinical sites in Buenos Aires will be included in the protocol and randomized to standard of care (SOC) or pharmacological adaptation (PA) -PA: PG + TDM. For the pharmacogenomics determination, we developed a multiplex approach including main polymorphisms of CYP2B6, CYP2A6, CYP3A4 y ABCB1 for efavirenz; and UGT1A1, ABCB1 and CYP3A4 for atazanavir. Drug plasma levels will be analyzed with ultra-performance liquid chromatography (UPLC). The main outcomes are to establish the usefulness of PG and TDM in determining the efficacy, safety and cost/effectiveness of a first-line antiretroviral therapy containing either efavirenz or atazanavir in patients with HIV infection who have not received prior antiretroviral therapy.
Blood pressure variation and the risk of essential hypertension have an important genetic component. In most cases susceptibility to essential hypertension is likely determined by the action of more than one gene. The identification of genes causing susceptibility to hypertension is important, since it would give new tools for the diagnosis and enable better etiological classification and specific treatment of the disease. The innovation of this study is to use the response to antihypertensive therapy as an intermediate phenotype. In the study, each subject uses one of four antihypertensive drugs, each as a monotherapy in a rotational fashion, for 28 days in a randomized order. The antihypertensive drugs to be tested include a thiazide diuretic, a beta-adrenergic antagonist, an angiotensin-II receptor antagonist and a calcium channel blocker. The drugs that are selected for the study are "typical" representatives of their groups and long-acting, and the dosages are sufficient but well tolerable.