Study of Losartan in the Treatment of NAFLD in Children

Miriam Vos, MD

Status and phase: Completed; Phase 2

Conditions: NAFLD

Treatments: Drug: Losartan

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01913470

1R03DK096157-01 (U.S. NIH Grant/Contract)

1R03DK096157-01A1 (U.S. NIH Grant/Contract)

IRB00062895

Details and patient eligibility

About

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease among children and is closely associated with obesity and the metabolic syndrome. NAFLD increases risk of mortality and natural history studies of adults show that NAFLD is an independent risk factor for cardiovascular disease. Pediatric NAFLD is particularly concerning from a public health standpoint, as it represents an early and possibly more aggressive form of the disease. Currently there is no effective treatment for pediatric NAFLD.

Losartan is an orally-administered angiotensin II receptor antagonist which is currently on the market to treat high blood pressure. The renin-angiotensin-aldosterone (RAA) system has been shown to be important in many disease states including renal disease, cardiovascular disease, and NAFLD. Angiotensin antagonists are a class of medications that has been proposed as a novel treatment of NAFLD in part because they would treat both the factors increasing cardiovascular (CVD) risks as well as potentially improve steatosis, fibrosis and hepatic inflammation.

This study is a randomized, double-blinded, placebo-controlled pilot study to evaluate whether 8 weeks of Losartan will decrease inflammatory markers among children ages 12-19 with a current diagnosis of NAFLD. Efficacy will be assessed by improvement in alanine aminotransferase (ALT) from baseline. Secondary endpoints will include aspartate aminotransferase (AST), cytokeratin 18 levels, and fasting triglyceride levels among others. Safety will be assessed by the recording of adverse events, clinical laboratory parameters, vital signs and physical examinations.

Enrollment: 12 patients

Sex: All

Ages: 11 to 19 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body Mass Index (BMI) > 85th% for age and gender
• History of definite or borderline nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy using NASH Clinical Research Network (CRN) criteria
• At least 2 months of attempted lifestyle changes after liver biopsy
• Current ALT ≥ 3 times normal (69 U/L for girls, 78 U/L for boys) at enrollment
• Glomerular filtration rate (GRF) > 90
• Weight ≥ 62.5 kg

Exclusion criteria

• Other chronic illness requiring daily medication (except medications for mild mental illness, acid reflux, allergies, stable attention deficit hyperactivity disorder (ADHD), or asthma)
• Supplement or anti-oxidant therapy within past 2 weeks
• Renal insufficiency
• Cirrhosis and liver synthetic dysfunction (International Normalized Ratio ≥ 1.5)
• History of hypotension
• Diabetes (or fasting glucose > 125 mg/dL)
• Acute illness within past 2 weeks prior to enrollment (fever > 100.4ºF)
• Pregnancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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12 participants in 2 patient groups

Losartan then Placebo

Experimental group

Description:

0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks then placebo pill for 8 weeks

Treatment:

Drug: Losartan

Sugar pill

Experimental group

Description:

placebo pill taken for 8 weeks then 0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks

Treatment:

Drug: Losartan