Acute Myocardial InfarctionPhase 4NCT01501110
Effects of N-acetylcysteine on Low T3 Syndrome
A Phase 4 study testing N-acetylcysteine in people with Acute Myocardial Infarction and Euthyroid Sick Syndrome, run by Federal University of Rio Grande do Sul at 2 sites in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Myocardial Infarction, Euthyroid Sick Syndrome, Ischemic Heart Disease
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 2 sitesBrazil
- Study dates
- Nov 2011to Nov 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of acute myocardial infarction with less than 12 hours of evolution
- reperfusion therapy (primary angioplasty)
Who cannot join
- Thyroid disease
- Chronic renal disease with renal replacement therapy
- hepatic insufficiency
- immunosuppression
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90540001
Instituto de Cardiologia
Porto Alegre, Rio Grande do Sul, 90540001
About this study
Official title: Evaluation of the Effects of N-acetylcysteine on Thyroid Hormone Levels in the Low T3 Syndrome
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.
Read the 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.
- Being tested
- N-acetylcysteine
- Keywords
- Euthyroid Sick Syndrome, low T3 syndrome, deiodases, oxidative stress, ischemic heart disease
- Medical subject headings
- Euthyroid Sick Syndromes, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC, acetylcysteine
in infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours
| Study group | Role | What they receive |
|---|---|---|
| n-acetylcysteine | Active comparator | intra-venous infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours. Receives: Drug: N-acetylcysteine |
| no intervention | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum T3 Levels at 48 Hours
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionJul 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of Rio Grande do Sul
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital de Clinicas de Porto Alegre, Programa de pós-graduação em endocrinologia
- Responsible party
- Principal investigator, Josi Vidart, Federal University of Rio Grande do Sul
- Investigators
- Josi Vidart, Principal investigator, Federal University of Rio Grande do SulAna maia, Study director, Federal University of Rio Grande do Sul
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01501110
- Sponsor's protocol ID
- 110061
- Status last verified
- Mar 2015
- First submitted
- 25 Nov 2011
- Last updated
- 31 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21540553Boelen 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.
PubMed 21791567Maia 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.
PubMed 21415143Bello 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.
PubMed 19255297Koenig RJ. Modeling the nonthyroidal illness syndrome. Curr Opin Endocrinol Diabetes Obes. 2008 Oct;15(5):466-9. doi: 10.1097/MED.0b013e32830eb838.
PubMed 18769221Vidart 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.
PubMed 25148231
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effects of N-acetylcysteine on Thyroid Hormone Levels in the Low T3 Syndrome
- ClinicalTrials.gov ID
- NCT01501110
- Acronym / sponsor ID
- 110061
- Keywords
- Euthyroid Sick Syndrome, low T3 syndrome, deiodases, oxidative stress, ischemic heart disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Federal University of Rio Grande do SulUniversity, hospital or other
- Collaborators
- Hospital de Clinicas de Porto Alegre, Programa de pós-graduação em endocrinologia
- Study start
- Nov 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 29 Dec 2011 (estimated)
- Results
- Posted 31 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| n-acetylcysteine | Active comparator | Drug: N-acetylcysteineintra-venous infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours. |
| no intervention | No intervention | –No intervention |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- diagnosis of acute myocardial infarction with less than 12 hours of evolution
- reperfusion therapy (primary angioplasty)
Key exclusion criteria (4 listed)
- Thyroid disease
- Chronic renal disease with renal replacement therapy
- hepatic insufficiency
- immunosuppression
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NAC, acetylcysteinein infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours | Drug | n-acetylcysteine |
Primary outcome
Serum T3 Levels at 48 Hours
Time frame: 48 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21540553Wajner 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.
- Background: PubMed 21791567Boelen 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.
- Background: PubMed 21415143Maia 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.
- Background: PubMed 19255297Bello 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.
- Background: PubMed 18769221Koenig RJ. Modeling the nonthyroidal illness syndrome. Curr Opin Endocrinol Diabetes Obes. 2008 Oct;15(5):466-9. doi: 10.1097/MED.0b013e32830eb838.
- Derived from this study: PubMed 25148231Vidart 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.
- Information on euthyroid sick syndromeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Josi Vidart principal investigator
Federal University of Rio Grande do Sul
Ana maia study director
Federal University of Rio Grande do Sul
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing N-acetylcysteine in people with Acute Myocardial Infarction and Euthyroid Sick Syndrome, run by Federal University of Rio Grande do Sul at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum T3 Levels at 48 Hours (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01501110, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2015.