Losartan for the Treatment of Pediatric NAFLD

NCT03467217 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 9 STOP-NAFLDU01DK061730
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

NAFLD - Nonalcoholic Fatty Liver Disease

Keywords

Losartan; Nonalcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline

  Baseline and 24 weeks

• Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST

  Baseline and 24 weeks

• Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT

  Baseline and 24 weeks

• Change in ALT at 12 Weeks Compared to Baseline ALT

  Baseline and 12 weeks

• Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline.

  Baseline and 24 weeks

Study Arms (2)

Losartan potassium capsule

ACTIVE COMPARATOR

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

Placebo losartan capsule

PLACEBO COMPARATOR

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

Interventions

Losartan potassium DRUG

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

Also known as: losartan, Cozaar,

Losartan potassium capsule

Placebo losartan capsule DRUG

Matching placebo losartan oral capsule

Placebo losartan capsule

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (10)

University of California, San Diego

San Diego, California, 92103, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60611-2605, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Links

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

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Losartan

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Laura Wilson
• Organization: Johns Hopkins Bloomberg School of Public Health

lwilson9@jhu.edu

410-955-0719

Study Officials

• Edward Doo, MD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, investigators, clinical staff, and data monitoring committee will not have knowledge of the interventions assigned to individual participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 15, 2018
• Study Start: October 2, 2018
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: October 21, 2021
• Results First Posted: October 21, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data from this study may be requested from the NIDDK Central Repository (https://www.niddkrepository.org/search/study/) two years after the completion of the primary outcome.
• Access Criteria: Apply through the NIDDK Central Repository:

Locations

US (10)