Study of Losartan in the Treatment of NAFLD in Children
Condition: NAFLD
MeSH terms: Non-alcoholic Fatty Liver Disease
Intervention: Losartan
Intervention description: Oral tablet to be taken once daily at 0.4mg/kg/day (max 25mg) for one week and then increased to 0.8mg/kg/day (max 50mg) for 7 additional weeks.
Intervention MeSH terms: Losartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 11 Years
Maximum age: 19 Years
Healthy volunteers: No
Keywords: NAFLD; Non-alcoholic Fatty Liver Disease; Obesity; Pediatrics; Children; Losartan; Cozaar

Summary:

      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.
    

Eligibility criteria:

        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