Fatty Liver Disease in Obese Children

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02117700
• Other study ID #: NemoursCC
• Secondary ID: American Diabete
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: December 2020

Study information

• Verified date: October 2022
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2020
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 18 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease
• Obesity

Intervention

Dietary Supplement:
• N-acetyl cysteine 600 mg once/day
NAC 600 mg once/day + Placebo once/day for 16 weeks
• N-acetyl cysteine 600mg twice/day
N-acetyl cysteine 600 mg twice/day for 16 weeks

Other:
• Placebo twice/day
Placebo capsules twice/day for 16 weeks

Locations

Country	Name	City	State
United States	Nemours Children's Clinic/Alfred I duPont Hospital	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nemours Children's Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Biomarkers of cardiovascular disease from baseline and at 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.	Upto 16 weeks
Primary	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