Fatty Liver Disease in Obese Children

Study Overview
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Brief Summary
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Although weight reduction through physical activity-based interventions is the mainstay therapy for nonalcoholic fatty liver disease (NAFLD), its maintenance is difficult and typically unsuccessful. This affirms the extreme need for alternate and/or adjunct therapies. Although convincing data from animal studies and a few adult human studies on the benefits of a natural product, N-acetyl cysteine (NAC), in a variety of liver conditions including NAFLD have emerged, studies in children are scarce. Therefore, the aim of the study is to test the use NAC as an innovative approach to attenuate the progression of NAFD in obese children with biopsy proven NASH. The central hypothesis is that NAC supplementation will reduce liver fat and liver enzymes and ameliorate risk factors of cardiometabolic disease in children with NAFLD.

Detailed Description
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Physical activity (PA)-induced weight reduction, the suggested therapy for noalcoholic liver disease (NAFLD), is difficult and its maintenance is typically unsuccessful in children, affirming the acute need for alternative/adjunct therapies. Although few promising approaches have been reported, the benefits are incongruent and mostly marginal. N-acetyl cysteine (NAC), a derivative of the natural amino acid, cysteine, appears to be promising as an adjunct therapy to PA. Animal and a few adult human studies suggest NAC-induced attenuation of liver abnormalities, oxidative stress, insulin resistance and inflammation. The primary aim of the proposal is to determine in obese children with biopsy proven NASH and elevated liver enzymes the effect of NAC at two different doses on liver fat using magnetic resonance imaging (MRI), liver enzymes and risk factors of cardiometabolic disease. We hypothesize that NAC will produce beneficial effect on these parameters.

Official Title
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Effect of N-acetyl Cysteine on Non Alcoholic Fatty Liver Disease in Obese Children

Conditions
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Obesity, Nonalcoholic Fatty Liver Disease, Cardiovascular Disease

Intervention / Treatment
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* Dietary Supplement: N-acetyl cysteine 600 mg once/day
* Dietary Supplement: N-acetyl cysteine 600mg twice/day
* Other: Placebo twice/day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 7 years and older NASH confirmed in a previous biopsy HbAIc <6.4% ALT > 60 U/L or 1.5 times the upper limit of normal Exclusion Criteria: Chronic liver disease including alpha-1-antitrypsin deficiency, Wilson's disease, autoimmune and viral hepatitis Medications such as adrenergic β-blockers, steroids and other drugs known to interfere with the measurement of liver enzymes and risk factors for cardiovascular disease Heart disease, chronic renal disease, adrenal, hepatic or thyroid dysfunction; active malignancy; and anemia History of prior treatment with NAC Evidence of hypersensitivity/allergy to NAC Alcoholism or drug abuse and smoking Inter-current illness over 7 days before the study & surgery in the past 3 mo.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: N-acetyl cysteine-1<br>N-acetyl cysteine 600 mg once/day + Placebo once/day for 16 weeks | Dietary Supplement: N-acetyl cysteine 600 mg once/day<br>* NAC 600 mg once/day + Placebo once/day for 16 weeks<br>|
| Experimental: N-acetyl cysteine-2<br>N-acetyl cysteine 600 mg twice/day for 16 weeks | Dietary Supplement: N-acetyl cysteine 600mg twice/day<br>* N-acetyl cysteine 600 mg twice/day for 16 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo twice/day for 16 weeks | Other: Placebo twice/day<br>* Placebo capsules twice/day for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver fat (MRI) and ALT levels from baseline and at 16 weeks | The primary outcome will be sustained reduction in ALT level, defined as 50% or less of the baseline level or 40 U/L or less and significant changes in liver fat (MRI) at the end of the study. All measurements of biological factors will be performed in the post absorptive (fasted) state. | Upto 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatty liver, obesity, children, oxidative stress, antioxidants