Study of Losartan in the Treatment of NAFLD in Children

NCT ID: NCT01913470

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-12-31

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.

Conditions

NAFLD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Losartan then Placebo

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

Group Type: EXPERIMENTAL

Losartan

Intervention Type: DRUG

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.

Sugar pill

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

Group Type: EXPERIMENTAL

Losartan

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Cozaar; Losartan Potassium Tablets; Serial Number: 74193404

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

• Minimum Eligible Age: 11 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Children's Healthcare of Atlanta

OTHER

Sponsor Role: collaborator

Miriam Vos, MD

OTHER

Sponsor Role: lead

Responsible Party

Miriam Vos, MD

Assistant Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Miriam Vos, MD, MSPH

Role: PRINCIPAL_INVESTIGATOR

Emory University / Children's Healthcare of Atlanta

Locations

Emory University / Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29992039 (View on PubMed)

Other Identifiers

1R03DK096157-01A1

Identifier Type: NIH

Identifier Source: secondary_id

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1R03DK096157-01

Identifier Type: NIH

Identifier Source: secondary_id

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IRB00062895

Identifier Type: -

Identifier Source: org_study_id