Effects of N-acetylcysteine on Low T3 Syndrome

NCT ID: NCT01501110

Last Updated: 2015-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-11-30

Brief 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.

Detailed 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.

Conditions

Acute Myocardial Infarction; Euthyroid Sick Syndrome; Ischemic Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

n-acetylcysteine

intra-venous infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours.

Group Type: ACTIVE_COMPARATOR

N-acetylcysteine

Intervention Type: DRUG

in infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours

no intervention

No intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

N-acetylcysteine

in infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours

Intervention Type: DRUG

Other Intervention Names

NAC; acetylcysteine

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: collaborator

Programa de pós-graduação em endocrinologia

UNKNOWN

Sponsor Role: collaborator

Federal University of Rio Grande do Sul

OTHER

Sponsor Role: lead

Responsible Party

Josi Vidart

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Josi Vidart

Role: PRINCIPAL_INVESTIGATOR

Federal University of Rio Grande do Sul

Ana maia

Role: STUDY_DIRECTOR

Federal University of Rio Grande do Sul

Locations

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Instituto de Cardiologia

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 21540553 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21791567 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21415143 (View on PubMed)

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):1448-1454. doi: 10.1378/chest.08-1816. Epub 2009 Mar 2.

Reference Type: BACKGROUND

PMID: 19255297 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 18769221 (View on PubMed)

Vidart J, Wajner SM, Leite RS, Manica A, Schaan BD, Larsen PR, Maia AL. N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial. J Clin Endocrinol Metab. 2014 Dec;99(12):4537-45. doi: 10.1210/jc.2014-2192.

Reference Type: DERIVED

PMID: 25148231 (View on PubMed)

Related Links

http://emedicine.medscape.com/article/118651-overview

Information on euthyroid sick syndrome

Other Identifiers

110061

Identifier Type: -

Identifier Source: org_study_id