Cardiovascular Disease, Nonalcoholic Fatty Liver Disease, Obesity
Conditions
Keywords
fatty liver, obesity, children, oxidative stress, antioxidants
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTN-acetyl cysteine 600 mg once/day
NAC 600 mg once/day + Placebo once/day for 16 weeks
DIETARY_SUPPLEMENTN-acetyl cysteine 600mg twice/day
N-acetyl cysteine 600 mg twice/day for 16 weeks
OTHERPlacebo twice/day
Placebo capsules twice/day for 16 weeks
Sponsors
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo controlled randomized double blind
Eligibility
Sex/Gender
ALL
Age
7 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in liver fat (MRI) and ALT levels from baseline and at 16 weeks | Upto 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Biomarkers of cardiovascular disease from baseline and at 16 weeks | Upto 16 weeks | The secondary outcome will be attenuation of abnormal levels of biomarkers of cardiovascular disease such as markers of inflammation, oxidative stress and insulin resistance. All measurements of biological factors will be performed in the post absorptive (fasted) state. |
Countries
United States
Outcome results
None listed