Study of Losartan in the Treatment of NAFLD in Children

NAFLD Clinical Trial

Official title:

A Pilot Study of Losartan in the Treatment of Pediatric NAFLD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01913470
• Other study ID #: IRB00062895
• Secondary ID: 1R03DK096157-01A
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2013
• Last updated: December 8, 2015
• Start date: July 2013
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 19 Years

Eligibility

Inclusion Criteria:

• • Age 12 - 19 years at enrollment

• Body Mass Index (BMI) > 85th% for age and gender

• History of definite or borderline NASH (by histology)using NASH Clinical Research Network (CRN) criteria

• At least 3 months of attempted lifestyle changes after liver biopsy

• ALT = 3 times normal (69 U/L for girls, 78 U/L for boys) at enrollment

Exclusion Criteria:

• • Other chronic illness requiring daily medication

• Supplement or anti-oxidant therapy within past 4 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• NAFLD

Intervention

Drug:
• Losartan
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.

Locations

Country	Name	City	State
United States	Emory University / Children's Healthcare of Atlanta	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Miriam Vos, MD	Children's Healthcare of Atlanta, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in AST from baseline to week 8 and/or week 22		Baseline, Week 8, and Week 22	No
Primary	Change in ALT from baseline to week 8 and/or week 22	The principal objective of this blinded, placebo controlled, crossover pilot study is to evaluate whether 8 weeks of Losartan in children with Nonalcoholic steatohepatitis (NASH) will decrease inflammation as measured by ALT.	Baseline, Week 8, Week 22	No
Secondary	Changes in cholesterol and fatty acid levels		Week -4, Week 14, Week 22, and Week 28	No
Secondary	Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), insulin and glucose		Week -4, Week 14, Week 22, and Week 28	No
Secondary	Changes in Plasminogen activator inhibitor-1 (PAI-1)		Week -4, Week 0, Week 8, Week 14, Week 22, and Week 28	No