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A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.

ABSTRACT: Background:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children, and currently, there are no FDA-approved therapies. Plasminogen activator inhibitor-1 (PAI-1) is elevated in children with NAFLD and associated with increased disease severity. Losartan potassium (losartan) is an angiotensin II receptor blocker (ARB) that reduces PAI-1 production and improves insulin sensitivity that has been proposed as a treatment for pediatric NAFLD but has not previously been tested. Methods:This was an 8-week randomized, double-blind, placebo-controlled, phase 2a, crossover study (with a 6-week washout between conditions) for safety and preliminary efficacy of losartan 50 mg a day taken orally in 12 normotensive children with biopsy proven nonalcoholic steatohepatitis (NASH). Results:Twelve children enrolled in the study, and nine completed all visits. No changes in blood pressure or serious adverse events occurred during the study. Trends in improvement in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and homeostatic model assessment insulin resistance (HOMA-IR) were seen with losartan treatment compared to the placebo time-period. More participants decreased ALT on losartan as compared to placebo (89% [8 out 9] vs. 56% [5 out of 9], respectively). Conclusions:This data provides preliminary evidence that losartan treatment is safe over 8 weeks in children with NAFLD and supports consideration of larger studies to test its efficacy. Trial registration:URL and trial identification number: https://clinicaltrials.gov/show/NCT01913470, NCT01913470.Date registered: August 1, 2013.

SUBMITTER: Vos MB

PROVIDER: S-EPMC5987658 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.

Vos Miriam B MB Jin Ran R Konomi Juna V JV Cleeton Rebecca R Cruz Jessica J Karpen Saul S Rodriguez Dellys Soler DS Frediani Jennifer K JK McCracken Courtney C Welsh Jean J

Pilot and feasibility studies 20180605

<h4>Background</h4>Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children, and currently, there are no FDA-approved therapies. Plasminogen activator inhibitor-1 (PAI-1) is elevated in children with NAFLD and associated with increased disease severity. Losartan potassium (losartan) is an angiotensin II receptor blocker (ARB) that reduces PAI-1 production and improves insulin sensitivity that has been proposed as a treatment for pediatric NAFLD but has not previously ...[more]

PMID: 29992039

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Project description:BackgroundNicotinamide has been reported to protect against liver steatosis and metabolic imbalances in nonalcoholic fatty liver disease (NAFLD) in animal models.ObjectivesThe objective was to investigate the efficacy and safety of nicotinamide supplementation in diabetic NAFLD patients.DesignThis is a prospective randomized controlled open label study.MethodsSeventy diabetic NAFLD patients were randomly assigned either to the nicotinamide group (n = 35) who received nicotinamide 1000 mg once daily for 12 weeks in addition to their antidiabetic therapy or the control group (n = 35) who received their antidiabetic therapy only. The primary outcome was improvement in steatosis score, while secondary outcomes included assessment of liver stiffness, liver enzymes, lipid profile, insulin resistance, serum malondialdehyde, serum adiponectin, and patients' quality of life (QOL).ResultsOnly 61 patients completed the study; 31 in the nicotinamide group and 30 in the control group. Comparisons between groups and within groups revealed nonsignificant changes in steatosis and fibrosis scores. However, significant reduction was observed in liver enzymes with a median decrease in alanine transaminase of 26.6% versus 0.74% in nicotinamide and control groups, respectively. After 12 weeks of treatment, the nicotinamide group showed significantly lower levels of low-density lipoprotein cholesterol (p value = 0.004), total cholesterol (p value = 0.006), and insulin resistance marker (p value = 0.005) compared with control. Serum triglycerides, malondialdehyde, and adiponectin levels were all comparable between the two groups. Regarding QOL, a significant improvement was detected in the total scores and the activity and fatigue domains scores.ConclusionNicotinamide at a dose of 1000 mg daily was tolerable, improved metabolic abnormalities and QOL of diabetic NAFLD patients with no effect on liver fibrosis or steatosis.Trial registrationThe study was registered at clinicaltrials.gov and given the ID number: 'NCT03850886'. https://clinicaltrials.gov/ct2/show/NCT03850886.

Dataset Information

A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.

Publications

A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.

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