Selenium Treatment and Chagasic Cardiopathy (STCC)

Sponsor

Oswaldo Cruz Foundation (Other)

Overall Status

Unknown status

CT.gov ID

NCT00875173

Collaborator

Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other), Ministry of Health, Brazil (Other)

130

Enrollment

Location

Arms

146

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Chagasic myocardiopathy caused by the protozoa Trypanosoma cruzi has been the principal cause of cardiac death in Latin America. Without any trypanocidal therapeutic intervention, infected subjects can pass from the indeterminate to the cardiac form with heart dysfunction. Our group has studied the role and the effect of the supplementation with the essential micronutrient selenium (Se) on T. cruzi infection, and the investigators have verified that:

low Se levels is related to the severity of the myocardiopathy in chagasic patients
adequate Se diet is essential for mice survival at the acute phase of the experimental

cruzi infection

Se supplementation prevented the myocardial lesions at the acute phase in mice. From these findings and considering that Se supplementation was able to prevent Keshan cardiopathy, to revert electrocardiographic and echocardiographic alterations in patients nourished by parenteral route, and reduced re-infarction and cardiac deaths from acute myocardial infarction; the investigators purpose to investigate if Se treatment via oral route, is able to impair the progress of heart dysfunction in chagasic patients expressed by the study of progression rate and by the comparison of the means of ventricular ejection fraction.

Methods:

The Selenium treatment and Chagasic Cardiopathy (STCC) trial is double-blind, placebo controlled, randomized in 130 chagasic patients at the chronic phase following the inclusion criteria of (a) altered ECHO (LVEF between 0,35 % and 45 %), (b) age between 20 and 65 years, (c) randomly divided in two groups: Placebo (n=65) and Se (n=65). Patients of Se group will intake diary 100 µg Se as sodium selenite for 12 months. The primary endpoint is the reduction of 50 % in the progression rate of heart dysfunction, and the secondary endpoint is a partial or total reversion in electrocardiography alterations.

Conclusion:

This trial was recently approved by Brazilian Research Ethics Committee and will be conducted in accordance with the principles for human experimentation. If the investigators confirmed the benefit of Se treatment, a strategy of utilization a micronutrient in an adequate concentration as a treatment in diary diet can revolutionize the therapeutic for chagasic myocardiopathy.

Condition or Disease	Intervention/Treatment	Phase
Chagas Disease	Drug: Selenium Drug: Placebo (for Selenium)	Phase 3

Detailed Description

Several induced cardiomyopathy , Mycoplasma pneumonia-induced myocarditis, heart damage investigations have shown positive effects of Se on experimental models: cardiotoxicity induced by chemotherapics, ischemic cardiopathy, CVB3 and LP-BM5 (murine AIDS, retrovirus)-in reperfused heart, and in chagasic cardiopathy. In addition, beneficial effects of Se supplementation were reported in patients with myocardial infarct, Keshan disease, and cardiac dysfunction during HPN.

Our group has investigated the role and Se effect on infection by T. cruzi. By evaluating plasma Se levels in 170 chagasic patients, we discovered that the frequency of subjects with Se levels lower than normal was significantly higher in those with severe cardiopathy. Moreover, in this pioneering research, we found a positive correlation between Se levels and the LVEF, indicating that normal Se levels pave the way for efficient cardiac function. Later, we investigated if nutritional deficiency of this trace element interfered with the development of cardiopathy and the susceptibility to experimental T. cruzi infection. In that study, we found 100 % of mortality in Se deficient mice, while in the selenium adequate groups only 20% of the male and no female died even at 40 dpi. In addition, parasitemia levels of infected mice were not altered by Se deficiency, suggesting that the high susceptibility at the acute phase was not due to the parasite load. We later investigated if Se treatment could minimize the course of T. cruzi infection or the myocarditis in mice. We verified that the concentration of 4 ppm Se did not alter the resistance to infection but was able in preventing the increase of CK-MB levels in infected mice, indicating that Se helps to protect the heart from inflammatory damage driven by T. cruzi infection.

Currently, experimental and clinical trials concerning Se supplementation have been performed; however, to date, there is no trial regarding the use of this micronutrient as a treatment to protect cardiac function in chagasic patients with cardiopathy. The present clinical trial aims to study the effect of Se intervention on the progression rate of the cardiopathy in patients with mild or moderate HD (LVEF between 35 % and 45 %) in order to validate this new strategy of treatment. The HD will be expressed by the progression rate and by the comparison of means of the LVEF. In this context we will test the hypothesis that Se treatment is able to interfere with the progression of cardiac dysfunction in chronic chagasic patients. We expect the impediment of the progression of ventricular dysfunction in patients with mild HD, and the improvement of cardiac function in patients with moderate HD in the group of patients receiving Se therapy. This is the first clinical trial concerning this specific group of cardiac chagasic patients with mild or moderate HD.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Selenium Treatment and Chagasic Cardiopathy (STCC): A Prospective Randomized Trial in Patients With Chagas Disease

Study Start Date :

Oct 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Selenium Sodium selenite 100 micrograms in capsugel by mouth diary for 365 consecutive days	Drug: Selenium selenium as a drug according to Brazilian regulation laws Other Names: Antioxidant therapy
Active Comparator: Placebo Capsugel for placebo (selenium 100 micrograms capsugel) by mouth diary for 365 consecutive days	Drug: Placebo (for Selenium) Placebo with similar flavor, smell and colour. Other Names: control

Arm

Intervention/Treatment

Experimental: Selenium

Sodium selenite 100 micrograms in capsugel by mouth diary for 365 consecutive days

Drug: Selenium

selenium as a drug according to Brazilian regulation laws

Other Names:

Antioxidant therapy

Active Comparator: Placebo

Capsugel for placebo (selenium 100 micrograms capsugel) by mouth diary for 365 consecutive days

Drug: Placebo (for Selenium)

Placebo with similar flavor, smell and colour.

Other Names:

control

Outcome Measures

Primary Outcome Measures

Ejection fraction by echocardiography [Twice a year]

Secondary Outcome Measures

Electrocardiography [twice a year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

altered ECHO (LVEF between 0,35 % and 45 %)
age between 20 and 65 years

Exclusion Criteria:

patients > 65 years of age
smoke habit, patients with non-chagasic cardiopathy, live close to mineral deposit, metals industries and place with radioactive exposition, vegetarian
depressive psychological profile
pregnant or in lactating period
present or presented cancer or diabetes.
patients will be excluded if they take anti-convulsive medicines (Clozapine, Valproic Acid)