Effects of N-acetylcysteine on Low T3 Syndrome

Acute Myocardial Infarction Clinical Trial

Official title:

Evaluation of the Effects of N-acetylcysteine on Thyroid Hormone Levels in the Low T3 Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01501110
• Other study ID #: 110061
• Status: Completed
• Phase: Phase 4
• First received: November 25, 2011
• Last updated: March 30, 2015
• Start date: November 2011
• Est. completion date: November 2013

Study information

• Verified date: March 2015
• Source: Federal University of Rio Grande do Sul
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

The propose of this study is to determine whether N-acetylcysteine is effective in reversing the changes in thyroid hormones seen in critical illness, known as the low T3 syndrome.

Description:

The low T3 syndrome or nonthyroidal illness is characterized by low levels of T3, normal or high normal levels of rT3, low or normal levels of T4 and inappropriately normal or low levels of TSH. These changes affect up to 75% of patients and have prognostic implications.

Interleukin-6 (IL6) seems to have a causative role in the pathogenesis of nonthyroidal illness. There is evidence that the reduction in serum T3 was inversely associated with serum IL-6, while the rT3 have a positive association. The mechanism of action of cytokines on the metabolism of thyroid hormones has not been determined and the potential role of cytokines on the deiodases has been the focus of research.

In a cell culture model study, IL-6 was able to suppress the conversion of T4 to T3 by deiodases type 1 and 2 and stimulate the inactivation of T3 by deiodase type 3, a situation similar to nonthyroidal illness. The use of N-acetylcysteine prevented this alterations, been consistent with the hypothesis that IL6 inhibits the function of the deiodases by increasing the oxygen reactive species and by consuming gluthathione or some gluthathione dependent cofactor.

Considering the absence of human studies evaluating the use of N-acetylcysteine in nonthyroidal illness, the aim of this study is to investigate whether NAC has in vivo effect on changes of thyroid hormones.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: November 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• diagnosis of acute myocardial infarction with less than 12 hours of evolution

• reperfusion therapy (primary angioplasty)

Exclusion Criteria:

• Thyroid disease

• Chronic renal disease with renal replacement therapy

• hepatic insufficiency

• immunosuppression

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Coronary Artery Disease
• Euthyroid Sick Syndrome
• Euthyroid Sick Syndromes
• Heart Diseases
• Ischemic Heart Disease
• Myocardial Infarction
• Myocardial Ischemia
• Syndrome

Intervention

Drug:
• N-acetylcysteine
in infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande do Sul
Brazil	Instituto de Cardiologia	Porto Alegre	Rio Grande do Sul

Sponsors (3)

Lead Sponsor	Collaborator
Federal University of Rio Grande do Sul	Hospital de Clinicas de Porto Alegre, Programa de pós-graduação em endocrinologia

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Bello G, Pennisi MA, Montini L, Silva S, Maviglia R, Cavallaro F, Bianchi A, De Marinis L, Antonelli M. Nonthyroidal illness syndrome and prolonged mechanical ventilation in patients admitted to the ICU. Chest. 2009 Jun;135(6):1448-54. doi: 10.1378/chest.08-1816. Epub 2009 Mar 2. — View Citation

Boelen A, Kwakkel J, Fliers E. Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev. 2011 Oct;32(5):670-93. doi: 10.1210/er.2011-0007. Epub 2011 Jul 26. Review. — View Citation

Koenig RJ. Modeling the nonthyroidal illness syndrome. Curr Opin Endocrinol Diabetes Obes. 2008 Oct;15(5):466-9. doi: 10.1097/MED.0b013e32830eb838. Review. — View Citation

Maia AL, Goemann IM, Meyer EL, Wajner SM. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J Endocrinol. 2011 Jun;209(3):283-97. doi: 10.1530/JOE-10-0481. Epub 2011 Mar 17. Review. — View Citation

Wajner SM, Goemann IM, Bueno AL, Larsen PR, Maia AL. IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. J Clin Invest. 2011 May;121(5):1834-45. doi: 10.1172/JCI44678. Epub 2011 Apr 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum T3 Levels at 48 Hours		48 hours	No

External Links

•   Information on euthyroid sick syndrome
•   Programa de pós-graduação em endocrinologia