SNPMiner Trials by Shray Alag


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Report for SNP rs2472677

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 Individualized Antiretroviral Therapy: Impact of Pharmacogenetic and Therapeutic Drug Monitoring in the Safety and Efficacy of First Line Antiretroviral Therapy in Patients With HIV Infection

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.

NCT03385473 Pharmacogenetics HIV Drug Monitoring Genetic: Pharmacogenomic index Diagnostic Test: Therapeutic drug monitoring

For atazanavir: Polymorphisms of UGT1A1 (rs8175347), ABCB1 (rs10456542),polymorphisms of the steroid and xenobiotic receptor NR1 2 (rs2472677) TDM for Efavirenz (EFV) and Atazanavir (ATV): UPLC with diode arrangement and mass/mass detection.

Primary Outcomes

Description: Number of days between obtention of study samples and availability of test results (turnaround time)

Measure: Feasibility of implementation of a multicenter study to analyze pharmacological adequation and therapeutic drug monitoring of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection

Time: 48 Weeks

Secondary Outcomes

Description: Pharmacological Adequation arm of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection will show reduced frequency of adverse events when compared with the Standard Prescription arm.

Measure: Frequency of adverse events

Time: 48 Weeks

Description: Pharmacological Adequation arm of efavirenz or atazanavir performs equally to the standard of care arm. Viral load at 48 weeks aimed to be non inferior between arms, analyzed through FDA-recommended Snapshot approach.

Measure: Efficacy of antiretroviral treatment

Time: 48 weeks

Description: Pharmacological Adequation arm of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection shows a better cost/effectiveness profile than the standard of care approach. (Direct Cost analysis)

Measure: Cost/effectiveness compared in both arms

Time: 48 Weeks

2 Personalization of AntiTB Treatment: Evaluation of Pharmacological Determinants of Treatment Response

The aim of the study is to investigate the possible correlation of plasma drug concentrations with Time To Positivity (TTP) in liquid culture in patients with active pulmonary multi sensitive TB in the first two weeks of treatment. Secondary aims are: the correlation between plasma drug concentrations and hepato/neuro toxicity; the impact of different allelic variants on PK data, toxicity and TTP in liquid culture; the feasibility of using dried blood/plasma spots to measure plasma concentrations of anti-TB drugs and determine genetic polymorphisms.

NCT03416309 Tuberculosis, Pulmonary
MeSH:Tuberculosis Tuberculosis, Pulmonary

Analyzed SNPs will be: ABCB1 3435C>T (rs1045642), OATP1B1 521T>C (rs4149056) e OATP1B1 85-7793T>C (rs4149032), PXR 63396C>T (rs2472677), BsmI G>A (rs1544410).

Primary Outcomes

Description: Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the first week of treatment.

Measure: Correlation between AUC of RHZE and TTP

Time: 1 week from start of treatment

Description: Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the second week of treatment.

Measure: Correlation between AUC of RHZE and TTP

Time: 2 weeks from start of treatment

Secondary Outcomes

Description: Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with hepatotoxicity (increase of AST and/or ALT) and neurotoxicity (peripheral neuropathy)

Measure: Correlation between AUC of RHZE and toxicity

Time: 1 week and 2 weeks from start of treatment

Description: Investigate the impact of different allelic variants of NAT2, SLCO1B1, ABCB1, VDR on AUC of RHZE toxicity and TTP in liquid culture

Measure: Correlation between PG and AUC of RHZE

Time: 1 week and 2 weeks from start of treatment

Description: Assess the consistency of using dried plasma spots to measure plasma concentrations of anti-TB drugs comparing to plasma samples

Measure: Assess the consistency of results using of DPS for measuring the plasma drug concentrations

Time: 1 week and 2 weeks from start of treatment

Description: A pharmacometric model will be develop to correlate pharmacokinetics (AUC of RHZE) with the anti-TB treatment response (clinical and TTP) of the standard first-line anti-TB regimen.

Measure: Correlate AUC of RHZE with antiTB response

Time: 6 months after end of treatment

Description: A pharmacometric model will be develop to correlate PG with the anti-TB treatment response (clinical and TTP) of the standard first-line anti-TB regimen.

Measure: Correlate PG with antiTB response

Time: 6 months after end of treatment


HPO Nodes