Clinical Assessment, Neuroimaging and Immunomarkers in Chagas Disease Study (CLINICS) (CLINICS)

CHADSS: Chagas Disease Scan Study

The main purpose of the study is to determine noninvasive markers of brain involvement in Chagas disease. In a subgroup of patients with high intensity transient signals (HITS) on transcranial Doppler monitorization, the investigators aim to determine the efficacy and safety of aspirin in preventing microembolization in patients with no previous history of stroke. Specific aims are listed bellow:

(1) to establish brain magnetic resonance imaging markers of stroke risk in patients with Chagasic heart failure (HF); (2) to determine whether biomarkers can predict stroke risk in patients with Chagasic HF; and (3) to evaluate the efficacy of antiplatelet treatment in decreasing microembolization rate in patients with Chagasic HF.

Study Overview

• Status: Recruiting
• Conditions: Chagas Disease With Heart Failure
• Intervention / Treatment: Drug: Aspirin

Detailed Description

Stroke is an enormous international public health concern, particularly in the developing world where there are limited resources available to provide for an aging population. One of the main contributors to stroke incidence is the highly prevalent Chagas disease, a parasitic infection affecting an estimated 18 million individuals and a major cause of heart failure in Latin America. Chagas disease conveys stroke risk through two established mechanisms: structural cardiac disease and chronic inflammation. Although inflammation is associated with an increased risk of ischemic stroke and poorer outcome, its role has been largely linked to atherogenesis. Chronic inflammation can result in endothelial dysfunction and stimulate the hemostatic system, increasing systemic fibrin production and platelet activation. Brain atrophy has also been associated with chronic inflammation. Adults, young and old, who develop a secondary cardiomyopathy from Chagas are therefore at higher risk of cardioembolism and neurodegeneration. Stroke patients usually survive, but can be left with significant disability affecting their health status, productivity, and quality of life. These factors impact caregivers as well. Thus, the social and economic consequences of stroke are vast. During our R21 planning grant period, we were able to establish a collaborative infrastructure between the research groups in Brazil and the United States and collect preliminary data. We found an association between Chagas disease and stroke that was independent of cardiomyopathy. Cognitive impairment and brain atrophy were also associated with Chagas disease independently of cardiomyopathy. Biomarkers orosomucoid, neprilysin, interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) were identified as diagnostic and therapeutic targets in Chagas disease. As part of this phase, we will address three specific aims: (1) to establish brain magnetic resonance imaging markers of stroke risk in patients with Chagasic congestive heart failure (CM); (2) to determine whether biomarkers can predict stroke risk in patients with Chagasic CM; and (3) to evaluate the efficacy of antiplatelet treatment in decreasing microembolization rate in patients with Chagasic CM. The long-term goal of this project is to establish non-invasive methods of stroke risk stratification and prediction of stroke outcome in patients with Chagas disease. This work will also facilitate the development of novel anti-trypanosomal, anti-inflammatory, and antithrombotic strategies for stroke prevention and management in Brazil.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40110060
      • Recruiting
      • Hospital Universitario Professor Edgard Santos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of heart failure according to Framingham criteria
• Informed consent
• Age 18 years or above

Exclusion Criteria:

• Patients with a history of an untreated malignancy (except local skin cancers)
• Ischemic stroke (determined using the Questionnaire for Verifying Stroke-Free Status (QVSFS)
• Patients on renal dialysis or with end-stage hepatic dysfunction
• Acute infection/inflammation (Temperature > 101.5 F, and/or WBC> 15, 000)
• Inability to obtain informed consent from patient or next of kin
• Anticoagulant use (warfarin or heparin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin; Aspirin 300mg per day for 7 days in patients with HITS on transcranial Doppler monitorization	Drug: Aspirin
No Intervention: Best medical treatment; Best medical treatment including drugs for heart failure and hypertension will be given to both groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain magnetic resonance imaging lesions	Primary hypothesis is that silent brain infarcts, brain atrophy and white matter disease will be more common in patients with Chagas disease heart failure when compared to other etiologies of heart failure.	Baseline cross-sectional data
Biomarkers	Primary hypothesis is that serum biomarkers orosomucoid, neprilysin, interleukin-6 and matrix metalloproteinase-9 will be increased in Chagas disease heart failure when compared to other etiologies of heart failure	Baseline cross-sectional data
Proportion of high intensity transient signals on transcranial Doppler monitorization	Primary hypothesis is that the proportion of patients with high intensity transient signals (HITS) on one-hour transcranial Doppler monitorization after one-week treatment with 300mg aspirin and best medical treatment will be less when compared with best medical treatment without aspirin	One week

Collaborators and Investigators

• Sponsor: Federal University of Bahia
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 26, 2012

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; Heart failure; Dementia; Chagas disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Trypanosomiasis; Euglenozoa Infections; Heart Failure; Chagas Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: R01NS064905 (U.S. NIH Grant/Contract)