The Effect of N- Acetylcysteine on Inflammatory and Oxidative Stress Biomarkers

Study Overview
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Brief Summary
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Background: . Bipolar disorders and tobacco use disorder are top of the causes of disability and mortality worldwide Objective: The aim of this study was to evaluate N-acetyl-cysteine (NAC) as an adjunctive treatment in patients with bipolar .disorders and tobacco use disorder (TUD) , to determine whether NAC reduces alterations in biomarkers of inflammatory and oxidative stress Methods: This study will be conducted as a double-blind, randomized, placebo controlles add NAC or placebo for .bipolar disorders and tobacco use disorder at Londrina State University, Brazil.

Detailed Description
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Tobacco use disorder and bipolar disorders are top of the causes of disability and mortality worldwide. The aim of this study was to evaluate N-acetyl-cysteine (NAC) as an adjunctive treatment in patients with Tobacco use disorder with comorbid bipolar disorder ( (N=72 NAC/placebo ) recruited from outpatients smoking cessation unit at Londrina State University, Brazil. The design was a randomized, double-blind, placebo controlled clinical trial of 12 weeks of adjunctive treatment with N-acetyl-cysteine (NAC), 1800mg/day. Participants will be patients with bipolar disorders with and without TUD, they will allocated to one of two groups at random to receive NAC or placebo For the evaluation of oxidative stress biomarkers will be assess among others malondialdehyde (MDA), lipid hydroperoxide,nitric oxide metabolites (NOx), antioxidant potential total plasma (TRAP), advanced oxidation protein products (AOPP), superoxide dismutase (SOD), catalase, the total glutathione (GSH) and oxidized (GSSG), paraoxonase (PON 1) activity thiol group (SH-group).For the evaluation of inflammation biomarkers will be analyze : BDNF, GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6,IL-6R, IL-7, IL-8, Leptin, TNF-α, TNF-RI, TNF-RII, high-sensitivity C-reactive protein (hs-CRP), erythrocytes sedimentation rate (ESR), homocysteine, haptoglobin, albumin , uric acid and fibrinogen.

Official Title
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The Effect of N- Acetylcysteine on Inflammatory and Oxidative Stress Biomarkers in Patients With Tobacco Use Disorders and Bipolar Disorders ..

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Dietary Supplement: N-acetyl-cysteine (NAC)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in this study participants must be motivated smokers to stop tobacco use Age greater than or equal to 18 and less than 65 years Both sexes All races Capacity to consent to the study and carefully follow the guidelines and procedures and sign the term of free and informed consent . Will be included with comorbid bipolar, depressive and anxiety disorder with tobacco use by more than 20 cigarettes per day, and a control group without these mood disorders and without tobacco use disorder. Exclusion Criteria: We excluded any subjects with: abnormal blood values on the following laboratory tests: *hemogram, aspartate transaminase (AST), alanine transaminase (ALT), urea and creatinine other actual and life-time axis-I diagnoses (including schizophrenia, psycho-organic syndromes, delirium, dementia, amnestic, and other cognitive disorders) medical illness, including HIV and hepatitis B and C, (auto)immune disorders immune modulatory drugs, e.g. glucocorticoids and use of antioxidants. These situations can affect an inflammatory and / or immune process.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NAC ( baseline )and 12 week<br>subjects with tobacco use disorder (TUD) and bipolar disorders who will receive N-acetyl-cysteine (NAC) or placebo at baseline for a period of 12 weeks The participants with TUD (n=72) and they will receive a 1800mg per day of NAC or matching placebo . There will be asses laboratory examinations for inflammatory and oxidative stress biomarkers at baseline and at 12 week | Dietary Supplement: N-acetyl-cysteine (NAC)<br>* Patients will be randomly allocated into two groups, double-blind, to receive NAC or placebo for a period of 12 weeks. All groups remain receiving maintenance treatment in outpatient smokiing cessation. The dosage will be fixed 1800 mg/day of NAC administered in capsules taken 2 before breakfast and 2 before dinner is equal doses.<br>|
| Placebo Comparator: placebo ( baseline ) and 12 week<br>subjects with tobacco use disorders (TUD and bipolar disorders who will receive N-acetyl-cysteine (NAC) or placebo for a period of 12 weeks. The participants with TUD and bipolar disorders (n=72) and they will receive a 1800mg per day of NAC or matching placebo . There will be assessed laboratory examinations for inflammatory and oxidative stress biomarkers at baseline and at 12 week | Other: Placebo<br>* Patients will be randomly allocated into two groups, double-blind, to receive NAC or placebo for a period of 12 weeks. All groups remain receiving maintenance treatment in smoking cessation service<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of N- acetylcysteine on oxidative stress biomarkers in patients with tobacco use disorders and bipolar disorders | The design was a randomized, double-blind, placebo controlled clinical trial of 12 weeks of adjunctive treatment with N-acetyl-cysteine (NAC). For the evaluation of oxidative stress biomarkers will be assess among others malondialdehyde (MDA), lipid hydroperoxide,nitric oxide metabolites (NOx), antioxidant potential total plasma (TRAP), advanced oxidation protein products (AOPP), superoxide dismutase (SOD), catalase, the total glutathione (GSH) and oxidized (GSSG), paraoxonase (PON 1) activity thiol group (SH-group). | 12 weeks | 
| The effect of N- acetylcysteine on inflammatory in patients with tobacco use disorders and bipolar disorders | For the evaluation of inflammation biomarkers will be analyze : BDNF, GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6,IL-6R, IL-7, IL-8, Leptin, TNF-α, TNF-RI, TNF-RII, high-sensitivity C-reactive protein (hs-CRP), erythrocytes sedimentation rate (ESR), homocysteine, haptoglobin, albumin , uric acid and fibrinogen. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobacco use disorder and bipolar disorders, N-acetylcysteine, Oxidative stress, inflammation