Losartan for the Treatment of Pediatric NAFLD

NCT ID: NCT03467217

Last Updated: 2021-10-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-02

Study Completion Date

2020-06-30

Brief Summary

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

Detailed Description

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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.

Conditions

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NAFLD - Nonalcoholic Fatty Liver Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Participants, investigators, clinical staff, and data monitoring committee will not have knowledge of the interventions assigned to individual participants.

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Losartan potassium

Intervention Type DRUG

Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype

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.

Group Type PLACEBO_COMPARATOR

Placebo losartan capsule

Intervention Type DRUG

Matching placebo losartan oral capsule

Interventions

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Losartan potassium

Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype

Intervention Type DRUG

Placebo losartan capsule

Matching placebo losartan oral capsule

Intervention Type DRUG

Other Intervention Names

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losartan, Cozaar,

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edward Doo, MD

Role: STUDY_DIRECTOR

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Locations

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University of California, San Diego

San Diego, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern Univ-Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

St. Louis University

St Louis, Missouri, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Parental Permission Form

View Document

Document Type: Informed Consent Form: Child Assent Form

View Document

Document Type: Informed Consent Form: HIPAA Authorization Form

View Document

Related Links

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http://jhuccs1.us/nash/open/centers/centers.htm

Nonalcoholic Steatohepatitis Clinical Research Network Centers

http://www2.niddk.nih.gov/

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Other Identifiers

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U01DK061730

Identifier Type: NIH

Identifier Source: secondary_id

View Link

9 STOP-NAFLD

Identifier Type: -

Identifier Source: org_study_id