Fatty Liver Disease in Obese Children

Sponsor

Nemours Children's Clinic (Other)

Overall Status

Unknown status

CT.gov ID

NCT02117700

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity Nonalcoholic Fatty Liver Disease Cardiovascular Disease	Dietary Supplement: N-acetyl cysteine 600 mg once/day Dietary Supplement: N-acetyl cysteine 600mg twice/day Other: Placebo twice/day	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

Apr 1, 2018

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.