Fatty Liver Disease in Obese Children

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Cardiovascular Disease; Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: N-acetyl cysteine 600 mg once/day; Dietary supplement: N-acetyl cysteine 600mg twice/day; Other: Placebo twice/day

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic/Alfred I duPont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetyl cysteine-1; N-acetyl cysteine 600 mg once/day + Placebo once/day for 16 weeks	Dietary supplement: N-acetyl cysteine 600 mg once/day; NAC 600 mg once/day + Placebo once/day for 16 weeks
Experimental: N-acetyl cysteine-2; N-acetyl cysteine 600 mg twice/day for 16 weeks	Dietary supplement: N-acetyl cysteine 600mg twice/day; N-acetyl cysteine 600 mg twice/day for 16 weeks
Placebo Comparator: Placebo; Placebo twice/day for 16 weeks	Other: Placebo twice/day; Placebo capsules twice/day for 16 weeks

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Nemours Children's Clinic
• Investigators: Principal Investigator: Babu Balagopal, PhD, Nemours Children's Clinic

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: April 16, 2014
• First Submitted That Met QC Criteria: April 17, 2014
• First Posted (Estimate): April 21, 2014

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: obesity; children; fatty liver; oxidative stress; antioxidants
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Cardiovascular Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: NemoursCC; American Diabetes Association (Other Grant/Funding Number: ADA1-14-CE-04)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No