Effect of statins on inflammation and cardiac function in patients with chronic Chagas disease: A protocol for pathophysiological studies in a multicenter, placebo-controlled, proof-of-concept phase II trial

PLoS One. 2023 Jan 13;18(1):e0280335. doi: 10.1371/journal.pone.0280335. eCollection 2023.

Abstract

Background: Cardiac complications, including heart failure and arrhythmias, are the leading causes of disability and death in Chagas disease (CD). CD, caused by the Trypanosoma cruzi parasite, afflicts 7 million people in Latin America, and its incidence is increasing in non-endemic countries due to migration. The cardiac involvement is explained by parasite-dependent, immune-mediated myocardial injury, microvascular abnormalities, and ischemia. Current treatment of early CD includes the administration of nifurtimox and benznidazole. However, their efficacy is low in the chronic phase and may induce severe adverse events, forcing therapy to halt. Therefore, finding innovative approaches to treat this life-threatening tropical disease is of utmost importance. Thus, improving the efficacy of the current antichagasic drugs by modifying the inflammatory response would render the current treatment more effective. It has been reported that, in mice, simvastatin decreases cardiac inflammation and endothelial activation, and improves cardiac function, effects that require clinical confirmation.

Objective: The study aims to analyze whether two doses of Atorvastatin, administered after CD treatment is completed, are safe and more efficacious than the antiparasitic drugs alone in reducing general inflammation and improving endothelial and cardiac functions in a proof-of-concept, placebo-controlled phase II trial.

Methods: 300 subjects will be recruited from four Chilean hospitals with an active Program for the Control of Chagas Disease. 40 or 80 mg/day of atorvastatin or placebo will be administered after completion of the antichagasic therapy. The patients will be followed up for 12 months. Efficacy will be determined by measuring changes in plasma levels of anti-inflammatory and pro-inflammatory cytokines, soluble cell adhesion molecules, BNP, and cTnT. Also, the resting 12-lead ECG and a 2D-echocardiogram will be obtained to evaluate cardiac function.

Trial registration: ClinicalTrials.gov Identifier: NCT04984616.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin / therapeutic use
  • Chagas Disease* / drug therapy
  • Chagas Disease* / parasitology
  • Clinical Trials, Phase II as Topic
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Multicenter Studies as Topic
  • Nitroimidazoles*
  • Persistent Infection
  • Randomized Controlled Trials as Topic
  • Trypanocidal Agents* / pharmacology
  • Trypanocidal Agents* / therapeutic use
  • Trypanosoma cruzi*

Substances

  • Atorvastatin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Nitroimidazoles
  • Trypanocidal Agents

Associated data

  • ClinicalTrials.gov/NCT04984616

Grants and funding

CC: 11201312 Agencia Nacional de Investigacion - FONDECYT iniciación - Chile JDM, 1210359 Agencia Nacional de Investigacion - FONDECYT regular - Chile UK: 1220105, Agencia Nacional de Investigacion - FONDECYT regular - Chile FG: 21170427, Agencia Nacional de Investigacion - Becas Doctorado - Chile The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.