Study of Losartan in the Treatment of NAFLD in Children

NCT01913470 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB000628951R03DK096157-01A11R03DK096157-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

NAFLD; Non-alcoholic Fatty Liver Disease; Obesity; Pediatrics; Children; Losartan; Cozaar

Outcome Measures

Primary Outcomes (1)

• Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)

  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 (Weeks 0 and 14), Endpoint (Weeks 8 and 22)

Secondary Outcomes (5)

• Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment)

  Baseline (Week 0 and 14), End of treatment (Week 8 and 22)

• Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment)

  Baseline (Week 0 and 14), End of treatment (Week 8 and 22)

• Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment)

  Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)

• Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment)

  Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)

• Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment

  Baseline, Week 8, Week 14, Week 22

Other Outcomes (1)

• Change in Aspartate Aminotransferase (AST) From Baseline to End of Treatment

  Baseline, Week 8, Week 14, and Week 22

Study Arms (2)

Losartan then Placebo

EXPERIMENTAL

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

Drug: Losartan

Sugar pill

EXPERIMENTAL

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

Drug: Losartan

Interventions

Losartan 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.

Also known as: Cozaar, Losartan Potassium Tablets, Serial Number: 74193404

Losartan then Placebo; Sugar pill

Eligibility Criteria

• Age: 11 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Miriam Vos, MD: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Children's Healthcare of Atlanta: collaborator

Study Sites (1)

Emory University / Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 29992039 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Losartan

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Miriam Vos, MD, MSPH
• Organization: Emory University

mvos@emory.edu

404-727-9930

Study Officials

• Miriam Vos, MD, MSPH

  Emory University / Children's Healthcare of Atlanta

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: August 1, 2013
• Study Start: July 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 15, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-04

Locations

US (1)