New chemotherapy regimens and biomarkers for Chagas disease

恰加斯病的新化疗方案和生物标志物

基本信息

  • 批准号:
    10557245
  • 负责人:
  • 金额:
    $ 91.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.
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:
  • 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
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{{ truncateString('IGOR C ALMEIDA', 18)}}的其他基金

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:
    10219078
  • 财政年份:
    2018
  • 资助金额:
    $ 91.62万
  • 项目类别:
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:
    9764253
  • 财政年份:
    2018
  • 资助金额:
    $ 91.62万
  • 项目类别:
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:
    10469327
  • 财政年份:
    2018
  • 资助金额:
    $ 91.62万
  • 项目类别:
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:
    9484015
  • 财政年份:
    2018
  • 资助金额:
    $ 91.62万
  • 项目类别:
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:
    9980275
  • 财政年份:
    2018
  • 资助金额:
    $ 91.62万
  • 项目类别:
BIOMOLECULE ANALYSIS CORE FACILITY
生物分子分析核心设施
  • 批准号:
    8357078
  • 财政年份:
    2011
  • 资助金额:
    $ 91.62万
  • 项目类别:
BIOMOLECULE ANALYSIS CORE FACILITY
生物分子分析核心设施
  • 批准号:
    8166186
  • 财政年份:
    2010
  • 资助金额:
    $ 91.62万
  • 项目类别:
Molecular Composition and Function of Trypanosoma cruzi Shed Vesicles
克氏锥虫脱落囊泡的分子组成和功能
  • 批准号:
    8147543
  • 财政年份:
    2010
  • 资助金额:
    $ 91.62万
  • 项目类别:
Identification and Validation of Novel Antigenic Targets in Trypanosoma cruzi
克氏锥虫新抗原靶标的鉴定和验证
  • 批准号:
    7858084
  • 财政年份:
    2009
  • 资助金额:
    $ 91.62万
  • 项目类别:
BIOMOLECULE CHARACTERIZATION AND SEPARATION CORE FACILITY
生物分子表征和分离核心设施
  • 批准号:
    7959146
  • 财政年份:
    2009
  • 资助金额:
    $ 91.62万
  • 项目类别:

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