Fatty Liver Disease in Obese Children

NCT ID: NCT02117700

Last Updated: 2022-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-12-31

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.

Conditions

Obesity; Nonalcoholic Fatty Liver Disease; Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

N-acetyl cysteine-1

N-acetyl cysteine 600 mg once/day + Placebo once/day for 16 weeks

Group Type: EXPERIMENTAL

N-acetyl cysteine 600 mg once/day

Intervention Type: DIETARY_SUPPLEMENT

NAC 600 mg once/day + Placebo once/day for 16 weeks

N-acetyl cysteine-2

N-acetyl cysteine 600 mg twice/day for 16 weeks

Group Type: EXPERIMENTAL

N-acetyl cysteine 600mg twice/day

Intervention Type: DIETARY_SUPPLEMENT

N-acetyl cysteine 600 mg twice/day for 16 weeks

Placebo

Placebo twice/day for 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo twice/day

Intervention Type: OTHER

Placebo capsules twice/day for 16 weeks

Interventions

N-acetyl cysteine 600 mg once/day

NAC 600 mg once/day + Placebo once/day for 16 weeks

Intervention Type: DIETARY_SUPPLEMENT

N-acetyl cysteine 600mg twice/day

N-acetyl cysteine 600 mg twice/day for 16 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo twice/day

Placebo capsules twice/day for 16 weeks

Intervention Type: OTHER

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.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nemours Children's Clinic

OTHER

Sponsor Role: lead

Responsible Party

Babu Balagopal

Head, Obesity & Cardiovascular Research Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Babu Balagopal, PhD

Role: PRINCIPAL_INVESTIGATOR

Nemours Children's Clinic

Locations

Nemours Children's Clinic/Alfred I duPont Hospital

Jacksonville, Florida, United States

Countries

United States

Other Identifiers

American Diabetes Association

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NemoursCC

Identifier Type: -

Identifier Source: org_study_id