NAFLD | Study of Losartan in the Treatment of NAFLD in Children
NAFLD research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:LosartanOral 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.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Losartan then Placebo0.4mg/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
Sugar pillplacebo 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
Start Date: July 2013
Completed Date: December 2015
Phase: Phase 2
Primary Outcome: Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)
Secondary Outcome: Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment)
Study sponsors, principal investigator, and references
Principal Investigator: Miriam Vos, MD, MSPH
Lead Sponsor: Miriam Vos, MD
Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)