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STOP-NAFLD: Losartan for the Treatment of Pediatric NAFLD

Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
Overall Status
Terminated
CT.gov ID
NCT03467217
Collaborator
Johns Hopkins University (Other)
83
Enrollment
10
Locations
2
Arms
20.9
Actual Duration (Months)
8.3
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
83 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 :
Oct 2, 2018
Actual Primary Completion Date :
Jun 30, 2020
Actual Study Completion Date :
Jun 30, 2020

Arms and Interventions

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 Names:
  • 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

    Outcome Measures

    Primary Outcome Measures

    1. Change in Serum Alanine Aminotransferase (ALT) From Baseline. [Baseline and 24 weeks]

      Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.

    Secondary Outcome Measures

    1. Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in gamma-glutamyl transpeptidase (GGT), measured in U/L.

    2. Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST [Baseline and 24 weeks]

      Change from baseline in serum aspartate aminotransferase, measured in U/L.

    3. Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT [Baseline and 24 weeks]

      Relative change from baseline in serum ALT, measured in percentage of change.

    4. Change in ALT at 12 Weeks Compared to Baseline ALT [Baseline and 12 weeks]

      Change from baseline in ALT at 12 weeks, measured in U/L.

    5. Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline. [Baseline and 24 weeks]

      Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) measures insulin resistance, calculated by fasting insulin (umol/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.

    6. Change in Weight at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in weight, measured in kg.

    7. Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline. [Baseline and 24 weeks]

      Change from baseline in BMI, measured in kg/m^2.

    8. Change in Waist Circumference at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in waist circumference, measured in centimeters.

    9. Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in waist-to-hip ratio, measured as the circumference of the waist in centimeters divided by the circumference of the hips in centimeters.

    10. Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Pediatric Quality of Life Inventory (PedsQOL) version 4.0 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. The outcome is 24-week change from baseline in PedsQOL Physical Health Score, where higher values indicate improvement in quality of life.

    11. Frequency of Adverse Events Over 24 Weeks [Baseline and 24 weeks]

      Numbers of adverse events reported over 24 weeks.

    12. Change in Total Cholesterol at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in total cholesterol, measured in mg/dL

    13. Change in Triglycerides at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in triglycerides, measured in mg/dL

    14. Change in HDL Cholesterol at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in HDL cholesterol, measured in mg/dL

    15. Change in LDL Cholesterol at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Change from baseline in LDL cholesterol, measured in mg/dL

    16. Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline [Baseline and 24 weeks]

      Pediatric Quality of Life Inventory (PedsQOL) version 4.0 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. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales. The outcome is 24-week change from baseline in PedsQOL Psychosocial Health Score, where higher values indicate improvement in quality of life.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    8 Years to 17 Years
    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 investigational new drug (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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, San Diego San Diego California United States 92103
    2 University of California, San Francisco San Francisco California United States 94143
    3 Emory University Atlanta Georgia United States 30322
    4 Northwestern Univ-Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611-2605
    5 Indiana University Indianapolis Indiana United States 46202
    6 St. Louis University Saint Louis Missouri United States 63104
    7 Columbia University New York New York United States 10032
    8 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229-3039
    9 Texas Children's Hospital Houston Texas United States 77030
    10 University of Washington Seattle Washington United States 98195

    Sponsors and Collaborators

    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    • Johns Hopkins University

    Investigators

    • Study Director: Edward Doo, MD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    ClinicalTrials.gov Identifier:
    NCT03467217
    Other Study ID Numbers:
    • 9 STOP-NAFLD
    • U01DK061730
    First Posted:
    Mar 15, 2018
    Last Update Posted:
    Oct 21, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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)
    Losartan
    Nonalcoholic Fatty Liver Disease
    Additional relevant MeSH terms:
    Liver Diseases
    Fatty Liver
    Non-alcoholic Fatty Liver Disease
    Losartan

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Losartan Placebo
    Arm/Group Description 100 mg losartan once per day Matching placebo, taken once per day
    Period Title: Overall Study
    STARTED 43 40
    COMPLETED 33 34
    NOT COMPLETED 10 6

    Baseline Characteristics

    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule Total
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule Total of all reporting groups
    Overall Participants 43 40 83
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    14
    (2)
    13
    (2)
    13
    (2)
    Sex: Female, Male (Count of Participants)
    Female
    10
    23.3%
    6
    15%
    16
    19.3%
    Male
    33
    76.7%
    34
    85%
    67
    80.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    33
    76.7%
    33
    82.5%
    66
    79.5%
    Not Hispanic or Latino
    10
    23.3%
    7
    17.5%
    17
    20.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    4
    9.3%
    5
    12.5%
    9
    10.8%
    Asian
    0
    0%
    2
    5%
    2
    2.4%
    Native Hawaiian or Other Pacific Islander
    1
    2.3%
    0
    0%
    1
    1.2%
    Black or African American
    1
    2.3%
    0
    0%
    1
    1.2%
    White
    28
    65.1%
    25
    62.5%
    53
    63.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    9
    20.9%
    8
    20%
    17
    20.5%
    Alanine aminotransferase (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    115
    (50)
    126
    (61)
    120
    (55)
    Aspartate aminotransferase (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    59
    (26)
    70
    (38)
    64
    (33)
    Alkaline phosphate (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    192
    (114)
    202
    (99)
    197
    (106)
    y-Glutamyltransferase (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    53
    (44)
    51
    (28)
    52
    (37)
    Total bilirubin (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.6
    (0.3)
    0.6
    (0.3)
    0.6
    (0.3)
    Direct bilirubin (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.1
    (0.1)
    0.1
    (0.1)
    0.1
    (0.1)
    Total cholesterol (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    159
    (44)
    155
    (31)
    157
    (38)
    High-density lipoprotein (mg/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/uL]
    39
    (7)
    41
    (9)
    40
    (8)
    Low-density lipoprotein (mg/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/uL]
    91
    (40)
    92
    (22)
    91
    (32)
    Triglycerides (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    158
    (105)
    128
    (58)
    143
    (87)
    Fasting serum glucose (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    91
    87
    89
    Insulin (umol/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [umol/mL]
    29
    38
    32
    Homeostasis model assessment (HOMA) score of insulin resistance (mg/dL x umol/mL/405) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL x umol/mL/405]
    6.5
    8.3
    7.1
    Hemoglobin A1c (percentage of glycosylated hemoglobin) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of glycosylated hemoglobin]
    5.4
    (0.6)
    5.4
    (0.3)
    5.4
    (0.5)
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    165
    (9)
    165
    (9)
    165
    (9)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    95
    (17)
    96
    (19)
    95
    (18)
    Body-mass index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    34
    (5)
    35
    (5)
    35
    (5)
    Mid arm circumference (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    33
    (4)
    33
    (4)
    33
    (4)
    Waist circumference (cm) [Median (Standard Deviation) ]
    Median (Standard Deviation) [cm]
    108
    (11)
    111
    (11)
    110
    (11)
    Hip circumference (cm) [Median (Standard Deviation) ]
    Median (Standard Deviation) [cm]
    110
    (11)
    112
    (11)
    111
    (11)
    Waist to hip ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    0.99
    (0.06)
    0.99
    (0.06)
    0.99
    (0.06)
    Systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    121
    (9)
    119
    (9)
    120
    (9)
    Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    69
    (6)
    69
    (6)
    69
    (6)
    Pulse (beats per minute) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [beats per minute]
    79
    (13)
    80
    (13)
    79
    (13)
    Breath rate (breaths/minute) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [breaths/minute]
    18
    (3)
    19
    (4)
    19
    (3)
    Hemoglobin (g/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/dL]
    14.5
    (1.1)
    14.0
    (1.2)
    14.2
    (1.2)
    Hematocrit (percentage of hematocrit) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of hematocrit]
    43.2
    (3.3)
    42.0
    (3.4)
    42.6
    (3.4)
    MCV (fL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [fL]
    84.9
    (4.4)
    84.7
    (3.4)
    84.8
    (4.0)
    White blood cell count (WBC) (10^3 cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [10^3 cells/uL]
    7.2
    (1.5)
    8.6
    (2.4)
    7.9
    (2.1)
    Red blood cell count (RBC) (million cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [million cells/uL]
    509
    (39)
    496
    (37)
    503
    (39)
    Neutrophils (cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cells/uL]
    3541
    (1123)
    4231
    (1867)
    3869
    (1552)
    Lymphocytes (cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cells/uL]
    2656
    (727)
    3031
    (1003)
    2835
    (884)
    Monocytes (cells/uL) [Median (Standard Deviation) ]
    Median (Standard Deviation) [cells/uL]
    501
    (165)
    578
    (217)
    537
    (194)
    Eosinophils (cells/uL) [Median (Standard Deviation) ]
    Median (Standard Deviation) [cells/uL]
    297
    (245)
    278
    (249)
    288
    (245)
    Basophils (cells/uL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cells/uL]
    35
    (37)
    65
    (126)
    49
    (91)
    Platelet (1000 cells/mm^3) [Median (Standard Deviation) ]
    Median (Standard Deviation) [1000 cells/mm^3]
    277
    (57)
    311
    (66)
    293
    (64)
    Sodium (mEq/L) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mEq/L]
    140.0
    (2.0)
    139.7
    (2.0)
    139.9
    (2.0)
    Potassium (mEq/L) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mEq/L]
    4.1
    (0.3)
    4.2
    (0.2)
    4.2
    (0.3)
    Chloride (mEq/L) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mEq/L]
    103.9
    (2.7)
    102.9
    (2.5)
    103.4
    (2.6)
    Bicarbonate (mEq/L) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mEq/L]
    24.3
    (2.5)
    24.7
    (2.0)
    24.4
    (2.3)
    Calcium (mEq/L) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mEq/L]
    9.8
    (0.4)
    9.8
    (0.3)
    9.8
    (0.3)
    Blood urea nitrogen (mg/dL) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mg/dL]
    10.9
    (3.1)
    10.5
    (2.5)
    10.7
    (2.8)
    Creatinine (mg/dL) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mg/dL]
    0.56
    (0.14)
    0.56
    (0.13)
    0.56
    (0.14)
    Estimated glomerular filtration rate (eGFR) (mL/min/1.73m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL/min/1.73m^2]
    156
    (19)
    155
    (17)
    156
    (18)
    Prothrombin time (seconds) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [seconds]
    12.3
    (1.3)
    11.9
    (1.3)
    12.1
    (1.3)
    International normalized ratio (INR) (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    1.04
    (0.07)
    1.04
    (0.08)
    1.04
    (0.07)
    Uric acid (mg/dL) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mg/dL]
    6.6
    (1.7)
    6.6
    (1.5)
    6.6
    (1.6)
    C-reactive protein (mg/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/L]
    3.8
    (2.5)
    3.8
    (3.0)
    3.8
    (2.7)
    Time from liver biopsy (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    0.7
    (0.6)
    0.8
    (0.6)
    0.8
    (0.6)
    Nonalcoholic fatty liver disease (NAFLD) activity score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    4.6
    (1.5)
    4.4
    (1.2)
    4.5
    (1.4)
    Steatohepatitis Diagnosis (Count of Participants)
    NAFLD, not NASH
    15
    34.9%
    9
    22.5%
    24
    28.9%
    Borderline Zone 3
    9
    20.9%
    7
    17.5%
    16
    19.3%
    Borderline Zone 1
    11
    25.6%
    12
    30%
    23
    27.7%
    Definite steatohepatitis
    8
    18.6%
    12
    30%
    20
    24.1%
    Fibrosis stage (Count of Participants)
    Stage 0
    17
    39.5%
    7
    17.5%
    24
    28.9%
    Stage 1
    13
    30.2%
    20
    50%
    33
    39.8%
    Stage 2
    8
    18.6%
    5
    12.5%
    13
    15.7%
    Stage 3
    5
    11.6%
    8
    20%
    13
    15.7%
    Hepatocellular ballooning grade (Count of Participants)
    0 - None
    31
    72.1%
    27
    67.5%
    58
    69.9%
    1 - Few
    6
    14%
    10
    25%
    16
    19.3%
    2 - Many
    6
    14%
    3
    7.5%
    9
    10.8%
    Steatosis (Count of Participants)
    5-33%
    4
    9.3%
    6
    15%
    10
    12%
    34-66%
    13
    30.2%
    11
    27.5%
    24
    28.9%
    >66%
    26
    60.5%
    23
    57.5%
    49
    59%
    Lobular inflammation (Count of Participants)
    <2 under 20x magnification
    21
    48.8%
    17
    42.5%
    38
    45.8%
    2-4 under 20x magnification
    16
    37.2%
    21
    52.5%
    37
    44.6%
    >4 under 20x magnification
    6
    14%
    2
    5%
    8
    9.6%
    Portal inflammation (Count of Participants)
    None
    7
    16.3%
    5
    12.5%
    12
    14.5%
    Mild
    30
    69.8%
    28
    70%
    58
    69.9%
    More than mild
    6
    14%
    7
    17.5%
    13
    15.7%

    Outcome Measures

    1. Primary Outcome
    Title Change in Serum Alanine Aminotransferase (ALT) From Baseline.
    Description Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Results based on complete case analysis.
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [U/L]
    -5.3
    (51.4)
    -6.3
    (77.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .95
    Comments
    Method ANCOVA
    Comments Adjusted for baseline value of ALT.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    -30.6 to 32.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline
    Description Change from baseline in gamma-glutamyl transpeptidase (GGT), measured in U/L.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [U/L]
    -1.9
    (13.9)
    0.6
    (19.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.56
    Comments
    Method ANCOVA
    Comments Adjusted for baseline value of GGT.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.5
    Confidence Interval (2-Sided) 95%
    -11.0 to 6.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST
    Description Change from baseline in serum aspartate aminotransferase, measured in U/L.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [U/L]
    0.2
    (27.2)
    -4.5
    (37.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.53
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline AST value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.7
    Confidence Interval (2-Sided) 95%
    -10.3 to 19.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT
    Description Relative change from baseline in serum ALT, measured in percentage of change.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [percentage of change]
    2.7
    (43.8)
    -5.7
    (73.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.57
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline ALT value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.4
    Confidence Interval (2-Sided) 95%
    -20.8 to 37.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change in ALT at 12 Weeks Compared to Baseline ALT
    Description Change from baseline in ALT at 12 weeks, measured in U/L.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [mg/dL]
    -5.8
    (43.0)
    -19.3
    (38.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments Adjusted for the baseline ALT value.
    Statistical Test of Hypothesis p-Value 0.25
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.6
    Confidence Interval (2-Sided) 95%
    9.7 to 36.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline.
    Description Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) measures insulin resistance, calculated by fasting insulin (umol/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [mg/dL x uU/mL/405]
    4.5
    (8.1)
    1.1
    (5.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline HOMA-IR value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.4
    Confidence Interval (2-Sided) 95%
    0.0 to 6.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Change in Weight at 24 Weeks Compared to Baseline
    Description Change from baseline in weight, measured in kg.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [kg]
    4.4
    (4.2)
    3.9
    (4.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.64
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline weight value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -1.5 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline.
    Description Change from baseline in BMI, measured in kg/m^2.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [kg/m^2]
    0.8
    (1.2)
    0.8
    (1.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.98
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline BMI value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change in Waist Circumference at 24 Weeks Compared to Baseline
    Description Change from baseline in waist circumference, measured in centimeters.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [cm]
    2.6
    (5.4)
    0.1
    (6.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.10
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline waist circumference value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.4
    Confidence Interval (2-Sided) 95%
    -0.5 to 5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline
    Description Change from baseline in waist-to-hip ratio, measured as the circumference of the waist in centimeters divided by the circumference of the hips in centimeters.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [ratio]
    0.01
    (0.05)
    -0.01
    (0.06)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.08
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline waist-to-hip ratio.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.02
    Confidence Interval (2-Sided) 95%
    0.00 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline
    Description Pediatric Quality of Life Inventory (PedsQOL) version 4.0 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. The outcome is 24-week change from baseline in PedsQOL Physical Health Score, where higher values indicate improvement in quality of life.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [score on a scale]
    0.9
    (14.7)
    -2.2
    (13.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.29
    Comments
    Method ANCOVA
    Comments Adjusted for the baseline PedsQOL Physical Health score.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.1
    Confidence Interval (2-Sided) 95%
    -2.8 to 9.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Frequency of Adverse Events Over 24 Weeks
    Description Numbers of adverse events reported over 24 weeks.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Number [adverse events]
    44
    55
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method Exact conditional binomial test
    Comments
    13. Secondary Outcome
    Title Change in Total Cholesterol at 24 Weeks Compared to Baseline
    Description Change from baseline in total cholesterol, measured in mg/dL
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [mg/dL]
    -6.7
    (28.4)
    -4.1
    (25.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.64
    Comments
    Method ANCOVA
    Comments Adjusted for baseline total cholesterol value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -13.9 to 8.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Change in Triglycerides at 24 Weeks Compared to Baseline
    Description Change from baseline in triglycerides, measured in mg/dL
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [mg/dL]
    13.2
    (98.1)
    6.2
    (41.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.67
    Comments
    Method ANCOVA
    Comments Adjusted for baseline triglyceride value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.0
    Confidence Interval (2-Sided) 95%
    -25.6 to 39.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Change in HDL Cholesterol at 24 Weeks Compared to Baseline
    Description Change from baseline in HDL cholesterol, measured in mg/dL
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [mg/dL]
    -2.1
    (6.2)
    -1.1
    (4.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.45
    Comments
    Method ANCOVA
    Comments Adjusted for baseline HDL cholesterol value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -3.4 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Change in LDL Cholesterol at 24 Weeks Compared to Baseline
    Description Change from baseline in LDL cholesterol, measured in mg/dL
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [mg/dL]
    -6.7
    (29.2)
    -6.2
    (14.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.93
    Comments
    Method ANCOVA
    Comments Adjusted for baseline LDL cholesterol value.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -10.3 to 9.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline
    Description Pediatric Quality of Life Inventory (PedsQOL) version 4.0 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. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales. The outcome is 24-week change from baseline in PedsQOL Psychosocial Health Score, where higher values indicate improvement in quality of life.
    Time Frame Baseline and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Losartan Potassium Capsule Placebo Losartan Capsule
    Arm/Group Description 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. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype 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. Placebo losartan capsule: Matching placebo losartan oral capsule
    Measure Participants 33 34
    Mean (Standard Deviation) [score on a scale]
    2.7
    (12.2)
    -0.2
    (13.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Losartan Potassium Capsule, Placebo Losartan Capsule
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.29
    Comments
    Method ANCOVA
    Comments Adjusted for baseline PedsQOL Psychosocial Health score.
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 2.9
    Confidence Interval (2-Sided) 95%
    -2.5 to 20.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Adverse event data were collected over a time period of 36 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Losartan Placebo
    Arm/Group Description 100 mg losartan once per day Matching placebo, taken once per day
    All Cause Mortality
    Losartan Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/43 (0%) 0/40 (0%)
    Serious Adverse Events
    Losartan Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/43 (0%) 4/40 (10%)
    Hepatobiliary disorders
    Cholecystitis 0/43 (0%) 0 1/40 (2.5%) 1
    Infections and infestations
    Wound infection 0/43 (0%) 0 1/40 (2.5%) 1
    Psychiatric disorders
    Suicidal ideation 0/43 (0%) 0 1/40 (2.5%) 1
    Surgical and medical procedures
    Surgical and medication procedures - Other, bilateral knee surgery 0/43 (0%) 0 1/40 (2.5%) 1
    Other (Not Including Serious) Adverse Events
    Losartan Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 28/43 (65.1%) 25/40 (62.5%)
    Cardiac disorders
    Hypertension 0/43 (0%) 0 2/40 (5%) 2
    Hypotension 2/43 (4.7%) 2 0/40 (0%) 0
    Ear and labyrinth disorders
    Middle ear inflammation 1/43 (2.3%) 1 0/40 (0%) 0
    Otitis externa 0/43 (0%) 0 1/40 (2.5%) 1
    Gastrointestinal disorders
    Abdominal pain 2/43 (4.7%) 2 1/40 (2.5%) 1
    Diarrhea 2/43 (4.7%) 2 2/40 (5%) 2
    Dyspepsia 2/43 (4.7%) 2 1/40 (2.5%) 1
    Nausea 3/43 (7%) 3 5/40 (12.5%) 5
    Stomach pain 2/43 (4.7%) 2 1/40 (2.5%) 1
    Vomiting 1/43 (2.3%) 1 1/40 (2.5%) 1
    Flatulence 1/43 (2.3%) 1 0/40 (0%) 0
    General disorders
    Fatigue 1/43 (2.3%) 1 0/40 (0%) 0
    Fever 1/43 (2.3%) 1 1/40 (2.5%) 1
    Infections and infestations
    Conjunctivitis 0/43 (0%) 0 1/40 (2.5%) 1
    Rash, pustular 0/43 (0%) 0 1/40 (2.5%) 1
    Sinusitus 2/43 (4.7%) 2 1/40 (2.5%) 1
    Sore throat 1/43 (2.3%) 1 1/40 (2.5%) 1
    Viremia 0/43 (0%) 0 1/40 (2.5%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 1/43 (2.3%) 1 1/40 (2.5%) 1
    Flank pain 0/43 (0%) 0 1/40 (2.5%) 1
    Musculoskeletal and connective tissue disorder, other - knee injury, pain, bursitis 1/43 (2.3%) 1 0/40 (0%) 0
    Musculoskeletal and connective tissue disorder, other-slipped capital femoral epiphysis (SCFE) 0/43 (0%) 0 1/40 (2.5%) 1
    Myalgia 0/43 (0%) 0 1/40 (2.5%) 1
    Nervous system disorders
    Dizziness 5/43 (11.6%) 5 3/40 (7.5%) 4
    Headache 7/43 (16.3%) 7 7/40 (17.5%) 7
    Respiratory, thoracic and mediastinal disorders
    Cough 1/43 (2.3%) 1 1/40 (2.5%) 1
    Epistaxis 1/43 (2.3%) 1 0/40 (0%) 0
    Flu like symptoms 2/43 (4.7%) 2 0/40 (0%) 0
    Nasal congestion 0/43 (0%) 0 1/40 (2.5%) 1
    Pharyngitis 0/43 (0%) 0 1/40 (2.5%) 1
    Rhinorrhea 0/43 (0%) 0 1/40 (2.5%) 1
    Upper respiratory infection 2/43 (4.7%) 2 7/40 (17.5%) 9
    Surgical and medical procedures
    Surgical and medical procedures - Other, Rhinoseptoplasty 1/43 (2.3%) 1 0/40 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Laura Wilson
    Organization Johns Hopkins Bloomberg School of Public Health
    Phone 410-955-0719
    Email lwilson9@jhu.edu
    Responsible Party:
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    ClinicalTrials.gov Identifier:
    NCT03467217
    Other Study ID Numbers:
    • 9 STOP-NAFLD
    • U01DK061730
    First Posted:
    Mar 15, 2018
    Last Update Posted:
    Oct 21, 2021
    Last Verified:
    Sep 1, 2021