New chemotherapy regimens and biomarkers for Chagas disease

恰加斯病的新化疗方案和生物标志物

• 批准号: 10557245
• 负责人: IGOR C ALMEIDA
• 金额: $ 91.62万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557245
• 关键词: Acute; Adult; Adverse drug event; Adverse event; Affect; Aftercare; Age; Animals; Antibodies; Antigens; Antioxidants; Antiparasitic Agents; Appearance; Benznidazole; Biological Markers; Blood; Cardiomyopathies; Chagas Disease; Chemotherapy-Oncologic Procedure; Child; Chronic; Chronic Phase; Classification; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Country; Data; Disease; Dose; Drug Combinations; Drug Kinetics; Evaluation; Excretory function; Failure; Frequencies; Heart; Heat-Shock Proteins 70; Infant; Infection; Inflammatory; Latin America; Lytic; Measures; Nifurtimox; Oxidative Stress; Parasitemia; Parasites; Parasitology; Patients; Peptide antibodies; Peptides; Peripheral; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Play; Polysaccharides; Population; Proteins; Public Health; Reaction; Recombinant Proteins; Regimen; Reporting; Research Design; Role; Safety; Serology; Serum; Symptoms; Testing; Therapeutic; Thrombophilia; Treatment Protocols; Treatment outcome; Trypanosoma cruzi; aptamer; chemotherapy; chronic infection; cohort; detection method; diagnostic tool; drug efficacy; early detection biomarkers; experience; follow-up; improved; novel; novel diagnostics; prognosis biomarker; progression marker; response; seroconversion; standard care; success; therapy outcome; tool; treatment duration; treatment response

ABSTRACT Chagas disease is caused by the parasite, Trypanosoma cruzi, and affects millions of people in Latin America. Lately, Chagas disease has become an emerging worldwide public health issue due to globalization. Chagas disease has two phases: an initial acute phase, usually with nonspecific symptoms or asymptomatic, and a lifelong chronic phase, which is clinically silent or indeterminate in 60-70% of patients. However, 30-40% of chronic patients will eventually develop heart and/or digestive complications. Currently, the only approved drugs for treating Chagas disease are benznidazole (BZN) and nifurtimox (NFX). The efficacy of these drugs is variable and depends on the disease stage, drug dose, age of patients, and infecting T. cruzi strain(s). Treatment in the acute phase is effective with both drugs. However, the efficacy of these drugs in adults with chronic, long-established infections is significantly lower and variable. Moreover, the high rate of adverse events of these drugs has hampered their regular clinical use, thus <1% of patients are being treated. In this project, we propose to test four new dosing regimens of BZN and NFX. Our first hypothesis is that a lower frequency of BZN and NFX dosing, with standard or extended treatment duration, might have the same or better efficacy than the standard treatment regimens with these drugs, with fewer adverse events. Here, we plan to analyze current and novel host- and parasite-derived BMKs that have shown promising results in pilot, full clinical trials or in animal studies, providing a measure of disease state and cure. Thus, our second hypothesis is that in those patients that respond to BZN or NFX treatment the serum levels of one or more proposed BMKs will be significantly reduced or become negative within three years post-treatment. To test these two hypotheses, we propose two specific aims: Specific Aim 1: To determine the safety and efficacy of extended benznidazole or nifurtimox treatment regimens with lower dosing frequency. Specific Aim 2: To evaluate host- and parasite-derived biomarkers for the follow-up of Chagas disease chemotherapy. The information gained in this project would also allow for better-designed clinical trials with previously proposed drug combinations, in which BZN and NFX would play a central role.

摘要

项目成果

A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.

• DOI: 10.3390/molecules27175714
• 发表时间: 2022-09-05
• 期刊: Molecules (Basel, Switzerland)

New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia.

• DOI: 10.1136/bmjopen-2021-052897
• 发表时间: 2021-12-31
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Alonso-Vega C;Urbina JA;Sanz S;Pinazo MJ;Pinto JJ;Gonzalez VR;Rojas G;Ortiz L;Garcia W;Lozano D;Soy D;Maldonado RA;Nagarkatti R;Debrabant A;Schijman A;Thomas MC;López MC;Michael K;Ribeiro I;Gascon J;Torrico F;Almeida IC
• 通讯作者: Almeida IC