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Losartan for the Treatment of Pediatric NAFLD (STOP-NAFLD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03467217
Recruitment Status : Recruiting
First Posted : March 15, 2018
Last Update Posted : November 19, 2019
Johns Hopkins University
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary:
A multicenter, randomized, double masked, placebo-controlled, parallel treatment groups phase 2 trial of losartan for pediatric nonalcoholic fatty liver disease (NAFLD).

Condition or disease Intervention/treatment Phase
NAFLD - Nonalcoholic Fatty Liver Disease Drug: Losartan potassium Drug: Placebo losartan capsule Phase 2

Detailed Description:
Children ages 8-17 years weighing between 70 -149 kilograms will be enrolled and treated with losartan (100 mg orally once per day) or matching placebo for 24 weeks. The hypothesis is that losartan will improve serum alanine aminotransferase (ALT) in children with pediatric NAFLD.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Participants, investigators, clinical staff, and data monitoring committee will not have knowledge of the interventions assigned to individual participants.
Primary Purpose: Treatment
Official Title: Losartan for the Treatment of Pediatric NAFLD (STOP-NAFLD): A Phase 2, Randomized, Placebo-Controlled Clinical Trial
Actual Study Start Date : October 2, 2018
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : February 28, 2021

Arm Intervention/treatment
Active Comparator: Losartan potassium capsule
Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to <150 kg.
Drug: Losartan potassium
Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype
Other Name: losartan, Cozaar,

Placebo Comparator: Placebo losartan capsule
Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to <150 kg.
Drug: Placebo losartan capsule
Matching placebo losartan oral capsule

Primary Outcome Measures :
  1. Change in serum alanine aminotransferase (ALT) from baseline. [ Time Frame: 24 weeks ]
    ALT value in U/L

Secondary Outcome Measures :
  1. Relative change in serum alanine aminotransferase (ALT) compared to baseline ALT [ Time Frame: 24 weeks ]
    ALT value in U/L

  2. Proportion of patients achieving normalization of ALT [ Time Frame: 24 weeks ]
    ALT value in U/L

  3. Change in serum aspartate aminotransferase AST at 24 weeks compared to baseline AST [ Time Frame: 24 weeks ]
    AST value in U/L

  4. Change in gamma-glutamyl transpeptidase (GGT) compared to baseline [ Time Frame: 24 weeks ]
    value in U/L

  5. Change in ALT at 12 weeks compared to baseline ALT [ Time Frame: 12 weeks ]
    ALT value in U/L

  6. Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) compared to baseline. [ Time Frame: 24 weeks ]
    is an equation which indicates the degree of insulin resistance, where higher scores equate to greater insulin resistance. HOMA-IR is calculated as fasting (Glucose (mmol/L) x insulin (pmol/L))/22.5. A HOMA-IR value >2.0 in prepubertal children and >2.6 in pubertal children, may be considered a warning sign for pediatricians to further investigate insulin resistance

  7. Change in Weight (kg) [ Time Frame: 24 weeks ]

  8. Change in Body-mass Index Z- Score [ Time Frame: 24 weeks ]
    Body mass index z-scores is calculated using age, gender, height and weight and calculated using 2000 CDC Growth Charts for norms.

  9. Change in Waist circumference [ Time Frame: 24 weeks ]

  10. Change in Waist -hip ratio [ Time Frame: 24 weeks ]
    ratio of the circumference of the waist to that of the hips. This is calculated as waist measurement divided by hip measurement (W ÷ H).

  11. Change in serum lipid profiles compared to baseline [ Time Frame: 24 weeks ]
    lipid profiles

  12. Change in Pediatric Quality of Life Inventory (PedsQL) Score scores compared to baseline [ Time Frame: 24 weeks ]
    Pediatric Quality of Life Inventory (PedsQL) version 4.0 is completed by both the child and parent/caregiver, and is composed of 23 items comprising 4 dimensions: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Scores are transformed on a scale from 0 to 100, with higher scores indicating better health-related quality of life. Physical Health Summary Score =Physical Functioning Scale Score. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales.

  13. Change in frequency of adverse events compared to baseline [ Time Frame: 24 weeks ]
    Numbers of adverse events reported

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 8-17 years at initial screening interview
  • Histological evidence of NAFLD with or without fibrosis and a NAFLD activity score (NAS) of ≥3, on a liver biopsy obtained no more than 730 days prior to enrollment.
  • Serum ALT at screening ≥ 50 IU/L

Exclusion Criteria:

  • Body weight less than 70 kg or greater than 150 kg at screening
  • Significant alcohol consumption or inability to reliably quantify alcohol intake
  • Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, other known hepatotoxins) for more than 2 consecutive weeks in the past year prior to randomization
  • New treatment with vitamin E or metformin started in the past 90 days or plans to alter the dose or stop over the next the 24 weeks. A stable dose is acceptable.
  • Prior or planned bariatric surgery
  • Uncontrolled diabetes (HbA1c 9.5% or higher)
  • Presence of cirrhosis on liver biopsy
  • History of hypotension or history of orthostatic hypotension
  • Stage 2 Hypertension or >140 systolic or >90 diastolic at screening
  • Current treatment with any antihypertensive medications including all angiotensin converting enzyme (ACE) inhibitors or aliskiren
  • Current treatment with potassium supplements or any drug known to increase potassium
  • Current daily use of nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Current treatment with lithium
  • Platelet counts below 100,000 /mm3
  • Clinical evidence of hepatic decompensation (serum albumin < 3.2 g/dL, international normalized ratio (INR) >1.3, direct bilirubin >1.3 mg/dL, history of esophageal varices, ascites, or hepatic encephalopathy)
  • Evidence of chronic liver disease other than NAFLD:

    • Biopsy consistent with histological evidence of autoimmune hepatitis
    • Serum hepatitis B surface antigen (HBsAg) positive.
    • Serum hepatitis C antibody (anti-HCV) positive.
    • Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 45% with histological evidence of iron overload
    • Alpha-1-antitrypsin (A1AT) phenotype/genotype ZZ or SZ
    • Wilson's disease
  • Serum alanine aminotransferase (ALT) greater than 300 IU/L
  • History of biliary diversion
  • History of kidney disease and/or estimated glomerular filtration rate (eGFR) < than 60 mL/min/1.73 m2 using Schwartz Bedside GFR Calculator for Children isotope dilution mass spectroscopy (IDMS)-traceable
  • Known Human Immunodeficiency Virus (HIV) infection
  • Active, serious medical disease with life expectancy less than 5 years
  • Active substance abuse including inhaled or injected drugs, in the year prior to screening
  • Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding
  • Participation in an IND trial in the 150 days prior to randomization
  • Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study
  • Inability to swallow capsules
  • Known allergy to losartan potassium or other angiotensin receptor blocker
  • Failure of parent or legal guardian to give informed consent or subject to give informed assent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03467217

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United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92103
Contact: Janis Durelle    619-543-5226   
Principal Investigator: Jeffrey Schwimmer, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Camille Langlois    415-476-1756   
Principal Investigator: Philip Rosenthal, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Miriam Vos, MD, MSPH    404-727-1463   
Contact: Rebecca Cleeton    (404) 727-5383   
Principal Investigator: Miriam Vos, MD, PhD         
United States, Illinois
Northwestern Univ-Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611-2605
Contact: Joy Ito    312-227-4559   
Contact: Mary Riordan    (312) 227.4558   
Principal Investigator: Mark Fishbein, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Ann Klipsch    317-274-9605   
Contact: Laura Walker    (317) 944-4490   
Principal Investigator: Jean Molleston, MD         
United States, Missouri
St. Louis University Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Theresa Cattoor, BSN,MA,CCRC    314-977-9335   
Principal Investigator: Ajay Jain, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Elena Reynoso    212-305-6274   
Principal Investigator: Joel Lavine, MD, PhD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: April Carr    513-803-7744   
Contact: Kimberlee Bernstein, BS, CCRP    (513)636-4406   
Principal Investigator: Stavra Xanthakos, MD         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Paula Hertel, MD    832-824-2099   
Contact: Alicia Lawson    (832) 824-3848   
Principal Investigator: Paula Hertel, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Melissa Young    206-987-1037   
Principal Investigator: Niviann Blondet, MD         
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Johns Hopkins University
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Study Director: Edward Doo, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT03467217     History of Changes
Other Study ID Numbers: 9 STOP-NAFLD
U01DK061730 ( U.S. NIH Grant/Contract )
First Posted: March 15, 2018    Key Record Dates
Last Update Posted: November 19, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: This study will comply with the NIH Data Sharing Policy and Results information from this trial will be submitted to and a public use database deposited with the NIDDK Central Repository.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: Data from this study may be requested from the NIDDK Central Repository ( two years after the completion of the primary outcome.
Access Criteria: Apply through the NIDDK Central Repository:

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Nonalcoholic Fatty Liver Disease
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action