Clinical trial NCT01913470: Study of Losartan in the Treatment of NAFLD in Children
Official title: A Pilot Study of Losartan in the Treatment of Pediatric NAFLD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NAFLD
Keywords: NAFLD
Non-alcoholic Fatty Liver Disease
Obesity
Pediatrics
Children
Losartan
Cozaar
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Children's Healthcare of Atlanta
First posted: 2013-08-01
Enrollment: 12
Sex: ALL
Minimum age (years): 11
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)
timeFrame: Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)
Secondary outcomes:
measure: Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment)
timeFrame: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)
measure: Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment)
timeFrame: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)
measure: Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment)
timeFrame: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)
measure: Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment)
timeFrame: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)
measure: Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment
timeFrame: Baseline, Week 8, Week 14, Week 22
Other outcomes:
measure: Change in Aspartate Aminotransferase (AST) From Baseline to End of Treatment
timeFrame: Baseline, Week 8, Week 14, and Week 22
Locations:
city: Atlanta
country: United States
facility: Emory University / Children's Healthcare of Atlanta
state: Georgia
Study officials:
affiliation: Emory University / Children's Healthcare of Atlanta
name: Miriam Vos, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vos MB, Jin R, Konomi JV, Cleeton R, Cruz J, Karpen S, Rodriguez DS, Frediani JK, McCracken C, Welsh J. A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease. Pilot Feasibility Stud. 2018 Jun 5;4:109. doi: 10.1186/s40814-018-0306-4. eCollection 2018.