Clinical trial NCT02117700: Fatty Liver Disease in Obese Children
Official title: Effect of N-acetyl Cysteine on Non Alcoholic Fatty Liver Disease in Obese Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Obesity
Nonalcoholic Fatty Liver Disease
Cardiovascular Disease
Keywords: fatty liver
obesity
children
oxidative stress
antioxidants
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
First posted: 2014-04-21
Enrollment: 14
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in liver fat (MRI) and ALT levels from baseline and at 16 weeks
timeFrame: Upto 16 weeks
Secondary outcomes:
Other outcomes:
measure: Change in Biomarkers of cardiovascular disease from baseline and at 16 weeks
timeFrame: Upto 16 weeks
Locations:
city: Jacksonville
country: United States
facility: Nemours Children's Clinic/Alfred I duPont Hospital
state: Florida
Study officials:
affiliation: Nemours Children's Clinic
name: Babu Balagopal, PhD
role: PRINCIPAL_INVESTIGATOR
References: