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

National Institutes of Health (NIH)

Status and phase: Terminated; Phase 2

Conditions: NAFLD - Nonalcoholic Fatty Liver Disease

Treatments: Drug: Losartan potassium; Drug: Placebo losartan capsule

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03467217

9 STOP-NAFLD

U01DK061730 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Enrollment: 83 patients

Sex: All

Ages: 8 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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83 participants in 2 patient groups, including a placebo group

Losartan potassium capsule

Active Comparator 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.

Treatment:

Drug: Losartan potassium

Placebo losartan capsule

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo losartan capsule