Losartan for the Treatment of Pediatric NAFLD

NAFLD - Nonalcoholic Fatty Liver Disease Clinical Trial

— STOP-NAFLD  

Official title:

Losartan for the Treatment of Pediatric NAFLD (STOP-NAFLD): A Phase 2, Randomized, Placebo-Controlled Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03467217
• Other study ID #: 9 STOP-NAFLD
• Secondary ID: U01DK061730
• Status: Terminated
• Phase: Phase 2
• Start date: October 2, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: September 2021
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 83
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• NAFLD - Nonalcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• Losartan potassium
Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype
• Placebo losartan capsule
Matching placebo losartan oral capsule

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Northwestern Univ-Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Columbia University	New York	New York
United States	St. Louis University	Saint Louis	Missouri
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Serum Alanine Aminotransferase (ALT) From Baseline.	Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.	Baseline and 24 weeks
Secondary	Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline	Change from baseline in gamma-glutamyl transpeptidase (GGT), measured in U/L.	Baseline and 24 weeks
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.	Baseline and 24 weeks
Secondary	Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT	Relative change from baseline in serum ALT, measured in percentage of change.	Baseline and 24 weeks
Secondary	Change in ALT at 12 Weeks Compared to Baseline ALT	Change from baseline in ALT at 12 weeks, measured in U/L.	Baseline and 12 weeks
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.	Baseline and 24 weeks
Secondary	Change in Weight at 24 Weeks Compared to Baseline	Change from baseline in weight, measured in kg.	Baseline and 24 weeks
Secondary	Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline.	Change from baseline in BMI, measured in kg/m^2.	Baseline and 24 weeks
Secondary	Change in Waist Circumference at 24 Weeks Compared to Baseline	Change from baseline in waist circumference, measured in centimeters.	Baseline and 24 weeks
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.	Baseline and 24 weeks
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.	Baseline and 24 weeks
Secondary	Frequency of Adverse Events Over 24 Weeks	Numbers of adverse events reported over 24 weeks.	Baseline and 24 weeks
Secondary	Change in Total Cholesterol at 24 Weeks Compared to Baseline	Change from baseline in total cholesterol, measured in mg/dL	Baseline and 24 weeks
Secondary	Change in Triglycerides at 24 Weeks Compared to Baseline	Change from baseline in triglycerides, measured in mg/dL	Baseline and 24 weeks
Secondary	Change in HDL Cholesterol at 24 Weeks Compared to Baseline	Change from baseline in HDL cholesterol, measured in mg/dL	Baseline and 24 weeks
Secondary	Change in LDL Cholesterol at 24 Weeks Compared to Baseline	Change from baseline in LDL cholesterol, measured in mg/dL	Baseline and 24 weeks
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.	Baseline and 24 weeks

External Links

•   Nonalcoholic Steatohepatitis Clinical Research Network Centers
•   The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)