NAFLD - Nonalcoholic Fatty Liver Disease
Conditions
Keywords
Losartan, Nonalcoholic Fatty Liver Disease
Brief summary
A multicenter, randomized, double masked, placebo-controlled, parallel treatment groups phase 2 trial of losartan for pediatric nonalcoholic fatty liver disease (NAFLD).
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.
Interventions
DRUGLosartan potassium
Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype
DRUGPlacebo losartan capsule
Matching placebo losartan oral capsule
Sponsors
Johns Hopkins University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Participants, investigators, clinical staff, and data monitoring committee will not have knowledge of the interventions assigned to individual participants.
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Change in Weight at 24 Weeks Compared to Baseline | Baseline and 24 weeks | Change from baseline in weight, measured in kg. |
| 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. |
| Change in Waist Circumference at 24 Weeks Compared to Baseline | Baseline and 24 weeks | Change from baseline in waist circumference, measured in centimeters. |
| 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. |
| 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. |
| Frequency of Adverse Events Over 24 Weeks | Baseline and 24 weeks | Numbers of adverse events reported over 24 weeks. |
| Change in Total Cholesterol at 24 Weeks Compared to Baseline | Baseline and 24 weeks | Change from baseline in total cholesterol, measured in mg/dL |
| Change in Triglycerides at 24 Weeks Compared to Baseline | Baseline and 24 weeks | Change from baseline in triglycerides, measured in mg/dL |
| Change in HDL Cholesterol at 24 Weeks Compared to Baseline | Baseline and 24 weeks | Change from baseline in HDL cholesterol, measured in mg/dL |
| Change in LDL Cholesterol at 24 Weeks Compared to Baseline | Baseline and 24 weeks | Change from baseline in LDL cholesterol, measured in mg/dL |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype | 43 |
| 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.
Placebo losartan capsule: Matching placebo losartan oral capsule | 40 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Clinic closed due to COVID-19 pandemic | 5 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Trial stopped early | 5 | 2 |
Baseline characteristics
| Characteristic | Losartan Potassium Capsule | Total | Placebo Losartan Capsule |
|---|---|---|---|
| Age, Continuous | 14 years STANDARD_DEVIATION 2 | 13 years STANDARD_DEVIATION 2 | 13 years STANDARD_DEVIATION 2 |
| Alanine aminotransferase | 115 U/L STANDARD_DEVIATION 50 | 120 U/L STANDARD_DEVIATION 55 | 126 U/L STANDARD_DEVIATION 61 |
| Alkaline phosphate | 192 U/L STANDARD_DEVIATION 114 | 197 U/L STANDARD_DEVIATION 106 | 202 U/L STANDARD_DEVIATION 99 |
| Aspartate aminotransferase | 59 U/L STANDARD_DEVIATION 26 | 64 U/L STANDARD_DEVIATION 33 | 70 U/L STANDARD_DEVIATION 38 |
| Basophils | 35 cells/uL STANDARD_DEVIATION 37 | 49 cells/uL STANDARD_DEVIATION 91 | 65 cells/uL STANDARD_DEVIATION 126 |
| Bicarbonate | 24.3 mEq/L STANDARD_DEVIATION 2.5 | 24.4 mEq/L STANDARD_DEVIATION 2.3 | 24.7 mEq/L STANDARD_DEVIATION 2 |
| Blood urea nitrogen | 10.9 mg/dL STANDARD_DEVIATION 3.1 | 10.7 mg/dL STANDARD_DEVIATION 2.8 | 10.5 mg/dL STANDARD_DEVIATION 2.5 |
| Body-mass index | 34 kg/m^2 STANDARD_DEVIATION 5 | 35 kg/m^2 STANDARD_DEVIATION 5 | 35 kg/m^2 STANDARD_DEVIATION 5 |
| Breath rate | 18 breaths/minute STANDARD_DEVIATION 3 | 19 breaths/minute STANDARD_DEVIATION 3 | 19 breaths/minute STANDARD_DEVIATION 4 |
| Calcium | 9.8 mEq/L STANDARD_DEVIATION 0.4 | 9.8 mEq/L STANDARD_DEVIATION 0.3 | 9.8 mEq/L STANDARD_DEVIATION 0.3 |
| Chloride | 103.9 mEq/L STANDARD_DEVIATION 2.7 | 103.4 mEq/L STANDARD_DEVIATION 2.6 | 102.9 mEq/L STANDARD_DEVIATION 2.5 |
| C-reactive protein | 3.8 mg/L STANDARD_DEVIATION 2.5 | 3.8 mg/L STANDARD_DEVIATION 2.7 | 3.8 mg/L STANDARD_DEVIATION 3 |
| Creatinine | 0.56 mg/dL STANDARD_DEVIATION 0.14 | 0.56 mg/dL STANDARD_DEVIATION 0.14 | 0.56 mg/dL STANDARD_DEVIATION 0.13 |
| Diastolic blood pressure | 69 mmHg STANDARD_DEVIATION 6 | 69 mmHg STANDARD_DEVIATION 6 | 69 mmHg STANDARD_DEVIATION 6 |
| Direct bilirubin | 0.1 mg/dL STANDARD_DEVIATION 0.1 | 0.1 mg/dL STANDARD_DEVIATION 0.1 | 0.1 mg/dL STANDARD_DEVIATION 0.1 |
| Eosinophils | 297 cells/uL STANDARD_DEVIATION 245 | 288 cells/uL STANDARD_DEVIATION 245 | 278 cells/uL STANDARD_DEVIATION 249 |
| Estimated glomerular filtration rate (eGFR) | 156 mL/min/1.73m^2 STANDARD_DEVIATION 19 | 156 mL/min/1.73m^2 STANDARD_DEVIATION 18 | 155 mL/min/1.73m^2 STANDARD_DEVIATION 17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants | 66 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 17 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting serum glucose | 91 mg/dL | 89 mg/dL | 87 mg/dL |
| Fibrosis stage Stage 0 | 17 Participants | 24 Participants | 7 Participants |
| Fibrosis stage Stage 1 | 13 Participants | 33 Participants | 20 Participants |
| Fibrosis stage Stage 2 | 8 Participants | 13 Participants | 5 Participants |
| Fibrosis stage Stage 3 | 5 Participants | 13 Participants | 8 Participants |
| Height | 165 cm STANDARD_DEVIATION 9 | 165 cm STANDARD_DEVIATION 9 | 165 cm STANDARD_DEVIATION 9 |
| Hematocrit | 43.2 percentage of hematocrit STANDARD_DEVIATION 3.3 | 42.6 percentage of hematocrit STANDARD_DEVIATION 3.4 | 42.0 percentage of hematocrit STANDARD_DEVIATION 3.4 |
| Hemoglobin | 14.5 g/dL STANDARD_DEVIATION 1.1 | 14.2 g/dL STANDARD_DEVIATION 1.2 | 14.0 g/dL STANDARD_DEVIATION 1.2 |
| Hemoglobin A1c | 5.4 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.6 | 5.4 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.5 | 5.4 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.3 |
| Hepatocellular ballooning grade 0 - None | 31 Participants | 58 Participants | 27 Participants |
| Hepatocellular ballooning grade 1 - Few | 6 Participants | 16 Participants | 10 Participants |
| Hepatocellular ballooning grade 2 - Many | 6 Participants | 9 Participants | 3 Participants |
| High-density lipoprotein | 39 mg/uL STANDARD_DEVIATION 7 | 40 mg/uL STANDARD_DEVIATION 8 | 41 mg/uL STANDARD_DEVIATION 9 |
| Hip circumference | 110 cm STANDARD_DEVIATION 11 | 111 cm STANDARD_DEVIATION 11 | 112 cm STANDARD_DEVIATION 11 |
| Homeostasis model assessment (HOMA) score of insulin resistance | 6.5 mg/dL x umol/mL/405 | 7.1 mg/dL x umol/mL/405 | 8.3 mg/dL x umol/mL/405 |
| Insulin | 29 umol/mL | 32 umol/mL | 38 umol/mL |
| International normalized ratio (INR) | 1.04 ratio STANDARD_DEVIATION 0.07 | 1.04 ratio STANDARD_DEVIATION 0.07 | 1.04 ratio STANDARD_DEVIATION 0.08 |
| Lobular inflammation 2-4 under 20x magnification | 16 Participants | 37 Participants | 21 Participants |
| Lobular inflammation <2 under 20x magnification | 21 Participants | 38 Participants | 17 Participants |
| Lobular inflammation >4 under 20x magnification | 6 Participants | 8 Participants | 2 Participants |
| Low-density lipoprotein | 91 mg/uL STANDARD_DEVIATION 40 | 91 mg/uL STANDARD_DEVIATION 32 | 92 mg/uL STANDARD_DEVIATION 22 |
| Lymphocytes | 2656 cells/uL STANDARD_DEVIATION 727 | 2835 cells/uL STANDARD_DEVIATION 884 | 3031 cells/uL STANDARD_DEVIATION 1003 |
| MCV | 84.9 fL STANDARD_DEVIATION 4.4 | 84.8 fL STANDARD_DEVIATION 4 | 84.7 fL STANDARD_DEVIATION 3.4 |
| Mid arm circumference | 33 cm STANDARD_DEVIATION 4 | 33 cm STANDARD_DEVIATION 4 | 33 cm STANDARD_DEVIATION 4 |
| Monocytes | 501 cells/uL STANDARD_DEVIATION 165 | 537 cells/uL STANDARD_DEVIATION 194 | 578 cells/uL STANDARD_DEVIATION 217 |
| Neutrophils | 3541 cells/uL STANDARD_DEVIATION 1123 | 3869 cells/uL STANDARD_DEVIATION 1552 | 4231 cells/uL STANDARD_DEVIATION 1867 |
| Nonalcoholic fatty liver disease (NAFLD) activity score | 4.6 units on a scale STANDARD_DEVIATION 1.5 | 4.5 units on a scale STANDARD_DEVIATION 1.4 | 4.4 units on a scale STANDARD_DEVIATION 1.2 |
| Platelet | 277 1000 cells/mm^3 STANDARD_DEVIATION 57 | 293 1000 cells/mm^3 STANDARD_DEVIATION 64 | 311 1000 cells/mm^3 STANDARD_DEVIATION 66 |
| Portal inflammation Mild | 30 Participants | 58 Participants | 28 Participants |
| Portal inflammation More than mild | 6 Participants | 13 Participants | 7 Participants |
| Portal inflammation None | 7 Participants | 12 Participants | 5 Participants |
| Potassium | 4.1 mEq/L STANDARD_DEVIATION 0.3 | 4.2 mEq/L STANDARD_DEVIATION 0.3 | 4.2 mEq/L STANDARD_DEVIATION 0.2 |
| Prothrombin time | 12.3 seconds STANDARD_DEVIATION 1.3 | 12.1 seconds STANDARD_DEVIATION 1.3 | 11.9 seconds STANDARD_DEVIATION 1.3 |
| Pulse | 79 beats per minute STANDARD_DEVIATION 13 | 79 beats per minute STANDARD_DEVIATION 13 | 80 beats per minute STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 17 Participants | 8 Participants |
| Race (NIH/OMB) White | 28 Participants | 53 Participants | 25 Participants |
| Red blood cell count (RBC) | 509 million cells/uL STANDARD_DEVIATION 39 | 503 million cells/uL STANDARD_DEVIATION 39 | 496 million cells/uL STANDARD_DEVIATION 37 |
| Sex: Female, Male Female | 10 Participants | 16 Participants | 6 Participants |
| Sex: Female, Male Male | 33 Participants | 67 Participants | 34 Participants |
| Sodium | 140.0 mEq/L STANDARD_DEVIATION 2 | 139.9 mEq/L STANDARD_DEVIATION 2 | 139.7 mEq/L STANDARD_DEVIATION 2 |
| Steatohepatitis Diagnosis Borderline Zone 1 | 11 Participants | 23 Participants | 12 Participants |
| Steatohepatitis Diagnosis Borderline Zone 3 | 9 Participants | 16 Participants | 7 Participants |
| Steatohepatitis Diagnosis Definite steatohepatitis | 8 Participants | 20 Participants | 12 Participants |
| Steatohepatitis Diagnosis NAFLD, not NASH | 15 Participants | 24 Participants | 9 Participants |
| Steatosis 34-66% | 13 Participants | 24 Participants | 11 Participants |
| Steatosis 5-33% | 4 Participants | 10 Participants | 6 Participants |
| Steatosis >66% | 26 Participants | 49 Participants | 23 Participants |
| Systolic blood pressure | 121 mmHg STANDARD_DEVIATION 9 | 120 mmHg STANDARD_DEVIATION 9 | 119 mmHg STANDARD_DEVIATION 9 |
| Time from liver biopsy | 0.7 years STANDARD_DEVIATION 0.6 | 0.8 years STANDARD_DEVIATION 0.6 | 0.8 years STANDARD_DEVIATION 0.6 |
| Total bilirubin | 0.6 mg/dL STANDARD_DEVIATION 0.3 | 0.6 mg/dL STANDARD_DEVIATION 0.3 | 0.6 mg/dL STANDARD_DEVIATION 0.3 |
| Total cholesterol | 159 mg/dL STANDARD_DEVIATION 44 | 157 mg/dL STANDARD_DEVIATION 38 | 155 mg/dL STANDARD_DEVIATION 31 |
| Triglycerides | 158 mg/dL STANDARD_DEVIATION 105 | 143 mg/dL STANDARD_DEVIATION 87 | 128 mg/dL STANDARD_DEVIATION 58 |
| Uric acid | 6.6 mg/dL STANDARD_DEVIATION 1.7 | 6.6 mg/dL STANDARD_DEVIATION 1.6 | 6.6 mg/dL STANDARD_DEVIATION 1.5 |
| Waist circumference | 108 cm STANDARD_DEVIATION 11 | 110 cm STANDARD_DEVIATION 11 | 111 cm STANDARD_DEVIATION 11 |
| Waist to hip ratio | 0.99 ratio STANDARD_DEVIATION 0.06 | 0.99 ratio STANDARD_DEVIATION 0.06 | 0.99 ratio STANDARD_DEVIATION 0.06 |
| Weight | 95 kg STANDARD_DEVIATION 17 | 95 kg STANDARD_DEVIATION 18 | 96 kg STANDARD_DEVIATION 19 |
| White blood cell count (WBC) | 7.2 10^3 cells/uL STANDARD_DEVIATION 1.5 | 7.9 10^3 cells/uL STANDARD_DEVIATION 2.1 | 8.6 10^3 cells/uL STANDARD_DEVIATION 2.4 |
| y-Glutamyltransferase | 53 U/L STANDARD_DEVIATION 44 | 52 U/L STANDARD_DEVIATION 37 | 51 U/L STANDARD_DEVIATION 28 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 40 |
| other Total, other adverse events | 28 / 43 | 25 / 40 |
| serious Total, serious adverse events | 0 / 43 | 4 / 40 |
Outcome results
Primary
Change in Serum Alanine Aminotransferase (ALT) From Baseline.
Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.
Time frame: Baseline and 24 weeks
Population: Results based on complete case analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Serum Alanine Aminotransferase (ALT) From Baseline. | -5.3 U/L | Standard Deviation 51.4 |
| Placebo Losartan Capsule | Change in Serum Alanine Aminotransferase (ALT) From Baseline. | -6.3 U/L | Standard Deviation 77.5 |
p-value: 0.9595% CI: [-30.6, 32.7]ANCOVA
Secondary
Change in ALT at 12 Weeks Compared to Baseline ALT
Change from baseline in ALT at 12 weeks, measured in U/L.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in ALT at 12 Weeks Compared to Baseline ALT | -5.8 mg/dL | Standard Deviation 43 |
| Placebo Losartan Capsule | Change in ALT at 12 Weeks Compared to Baseline ALT | -19.3 mg/dL | Standard Deviation 38.5 |
p-value: 0.2595% CI: [9.7, 36.7]ANCOVA
Secondary
Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline.
Change from baseline in BMI, measured in kg/m\^2.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline. | 0.8 kg/m^2 | Standard Deviation 1.2 |
| Placebo Losartan Capsule | Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline. | 0.8 kg/m^2 | Standard Deviation 1.3 |
p-value: 0.9895% CI: [-0.6, 0.6]ANCOVA
Secondary
Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline
Change from baseline in gamma-glutamyl transpeptidase (GGT), measured in U/L.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline | -1.9 U/L | Standard Deviation 13.9 |
| Placebo Losartan Capsule | Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline | 0.6 U/L | Standard Deviation 19.7 |
p-value: 0.5695% CI: [-11, 6]ANCOVA
Secondary
Change in HDL Cholesterol at 24 Weeks Compared to Baseline
Change from baseline in HDL cholesterol, measured in mg/dL
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in HDL Cholesterol at 24 Weeks Compared to Baseline | -2.1 mg/dL | Standard Deviation 6.2 |
| Placebo Losartan Capsule | Change in HDL Cholesterol at 24 Weeks Compared to Baseline | -1.1 mg/dL | Standard Deviation 4.9 |
p-value: 0.4595% CI: [-3.4, 1.5]ANCOVA
Secondary
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline.
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline. | 4.5 mg/dL x uU/mL/405 | Standard Deviation 8.1 |
| Placebo Losartan Capsule | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline. | 1.1 mg/dL x uU/mL/405 | Standard Deviation 5.2 |
p-value: 0.0595% CI: [0, 6.8]ANCOVA
Secondary
Change in LDL Cholesterol at 24 Weeks Compared to Baseline
Change from baseline in LDL cholesterol, measured in mg/dL
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in LDL Cholesterol at 24 Weeks Compared to Baseline | -6.7 mg/dL | Standard Deviation 29.2 |
| Placebo Losartan Capsule | Change in LDL Cholesterol at 24 Weeks Compared to Baseline | -6.2 mg/dL | Standard Deviation 14.8 |
p-value: 0.9395% CI: [-10.3, 9.4]ANCOVA
Secondary
Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline | 0.9 score on a scale | Standard Deviation 14.7 |
| Placebo Losartan Capsule | Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline | -2.2 score on a scale | Standard Deviation 13.3 |
p-value: 0.2995% CI: [-2.8, 9]ANCOVA
Secondary
Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline | 2.7 score on a scale | Standard Deviation 12.2 |
| Placebo Losartan Capsule | Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline | -0.2 score on a scale | Standard Deviation 13.9 |
p-value: 0.2995% CI: [-2.5, 20.1]ANCOVA
Secondary
Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST
Change from baseline in serum aspartate aminotransferase, measured in U/L.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST | 0.2 U/L | Standard Deviation 27.2 |
| Placebo Losartan Capsule | Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST | -4.5 U/L | Standard Deviation 37 |
p-value: 0.5395% CI: [-10.3, 19.8]ANCOVA
Secondary
Change in Total Cholesterol at 24 Weeks Compared to Baseline
Change from baseline in total cholesterol, measured in mg/dL
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Total Cholesterol at 24 Weeks Compared to Baseline | -6.7 mg/dL | Standard Deviation 28.4 |
| Placebo Losartan Capsule | Change in Total Cholesterol at 24 Weeks Compared to Baseline | -4.1 mg/dL | Standard Deviation 25.2 |
p-value: 0.6495% CI: [-13.9, 8.7]ANCOVA
Secondary
Change in Triglycerides at 24 Weeks Compared to Baseline
Change from baseline in triglycerides, measured in mg/dL
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Triglycerides at 24 Weeks Compared to Baseline | 13.2 mg/dL | Standard Deviation 98.1 |
| Placebo Losartan Capsule | Change in Triglycerides at 24 Weeks Compared to Baseline | 6.2 mg/dL | Standard Deviation 41.1 |
p-value: 0.6795% CI: [-25.6, 39.7]ANCOVA
Secondary
Change in Waist Circumference at 24 Weeks Compared to Baseline
Change from baseline in waist circumference, measured in centimeters.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Waist Circumference at 24 Weeks Compared to Baseline | 2.6 cm | Standard Deviation 5.4 |
| Placebo Losartan Capsule | Change in Waist Circumference at 24 Weeks Compared to Baseline | 0.1 cm | Standard Deviation 6.4 |
p-value: 0.195% CI: [-0.5, 5.3]ANCOVA
Secondary
Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline | 0.01 ratio | Standard Deviation 0.05 |
| Placebo Losartan Capsule | Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline | -0.01 ratio | Standard Deviation 0.06 |
p-value: 0.0895% CI: [0, 0.05]ANCOVA
Secondary
Change in Weight at 24 Weeks Compared to Baseline
Change from baseline in weight, measured in kg.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Change in Weight at 24 Weeks Compared to Baseline | 4.4 kg | Standard Deviation 4.2 |
| Placebo Losartan Capsule | Change in Weight at 24 Weeks Compared to Baseline | 3.9 kg | Standard Deviation 4.3 |
p-value: 0.6495% CI: [-1.5, 2.5]ANCOVA
Secondary
Frequency of Adverse Events Over 24 Weeks
Numbers of adverse events reported over 24 weeks.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan Potassium Capsule | Frequency of Adverse Events Over 24 Weeks | 44 adverse events |
| Placebo Losartan Capsule | Frequency of Adverse Events Over 24 Weeks | 55 adverse events |
p-value: 0.17Exact conditional binomial test
Secondary
Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT
Relative change from baseline in serum ALT, measured in percentage of change.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium Capsule | Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT | 2.7 percentage of change | Standard Deviation 43.8 |
| Placebo Losartan Capsule | Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT | -5.7 percentage of change | Standard Deviation 73.2 |
p-value: 0.5795% CI: [-20.8, 37.5]ANCOVA