Effect of Obesity on Proton Pump Inhibitors (LiverLabPPI)

Physiologic Determinants of PPI Disposition in Children

This longitudinal study tests the hypothesis that obesity affects drug pharmacology of acid suppression medications in children.

Study Overview

• Status: Completed
• Conditions: Pediatric Obesity; GERD; NAFLD
• Intervention / Treatment: Drug: Lansoprazole; Drug: Pantoprazole; Drug: Midazolam

Detailed Description

The purpose of this research study is to see how the body breaks down certain medicines. Many medicines are broken down in the liver. The liver is an organ in the belly. A person's age, size, genetics (DNA), and the health of their liver decide how quickly the body breaks down medicines and how much medication a person needs to take. Everybody's liver has some fat in it, but the amount of fat is different from person to person. The purpose of this study is to see if the amount of fat in the liver affects how quickly acid suppression medications start and stop working and get removed from the body.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Kansas City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 6-21 years of age

• Obese and non-obese individuals

  • BMI ≥10th percentile for age (6-20 years of age)
  • BMI ≥18.5 (>20 years of age)
• Otherwise healthy; or otherwise healthy with diagnosis of GERD, NAFLD, chronic abdominal pain or obesity, according to report of medical history and/or review of the medical record
• Receiving or not receiving pantoprazole or lansoprazole for routine medical care
• MRI Hoop Test Clearance

Exclusion Criteria:

• Unable or unwilling to give written permission/assent/consent
• For PO Study Drug: Any anatomic abnormality of the GI tract as defined by history, PE, or radiographic findings, including Bariatric surgery, Nissen fundoplication or equivalent surgery.
• For IV Study Drug: Any anatomic abnormality of the GI tract as defined by history, PE, or radiographic findings, except Bariatric surgery, Nissen fundoplication or equivalent surgery.
• For subjects undergoing weight management, treatment in the last 7 days with proton pump inhibitors omeprazole, esomeprazole, dexlansoprazole, or grapefruit juice.
• For subjects not undergoing weight management, treatment in the last 7 days with medications known to clinically significantly inhibit (e.g., omeprazole, esomeprazole, fluoxetine, fluvoxamine, ketoconazole, ticlopidine, felbamate, trazodone, valproic acid, topiramate) or induce (e.g., phenobarbital, carbamazepine, phenytoin) CYP2C19; and those known at therapeutic doses to significantly inhibit (e.g., erythromycin, clarithromycin, grapefruit juice, verapamil, diltiazem, cimetidine, ketoconazole) or induce (e.g., oxcarbazepine, carbamazepine, phenytoin, phenobarbital, St. John's Wort, rifampin, rifapentine) or CYP3A4 activity in the last 7 days.
• Unable to have blood drawn for the screening lab tests
• Unable or unwilling to fast overnight prior to the study session
• Unable to have blood drawn for the screening lab tests
• If taking lansoprazole or pantoprazole for clinical purposes, unable or unwilling to abstain from that PPI for 3 days prior to PK visit when the PPI is not the same as the study drug for that PK visit
• Metal in the body or any foreign bodies that precludes MRI sequencing
• Claustrophobia
• Exceeds 500lbs or 227 kg in Body Weight
• Demonstrated adverse reaction to previous pantoprazole or PPI exposure
• Impaired hepatic activity as determined by routine liver function testing and defined as values ≥ 5 times the age-specific upper limit of normal (ULN) for AST, ALT, total bilirubin >2.0mg/dl, alkaline phosphatase ≥ 5 times the age-specific ULN
• Impaired renal function defined as creatinine ≥ 3 times the age-specific ULN
• Females of child-bearing age who are pregnant or breast-feeding
• Any known infection with hepatitis B, C, or human immunodeficiency virus (HIV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Children enrolled to receive proton pump inhibitor; Evaluate the effect of liver fat on pharmacology of PPI's, and if applicable midazolam

Drug: Lansoprazole; single-dose administration. Administered to a subset of participants who agreed to receive this drug upon enrollment.; Drug: Pantoprazole; single-dose administration. Administered to a subset of participants who agreed to receive this drug upon enrollment.; Drug: Midazolam; single-dose administration. Administered to a subset of participants who agreed to receive this drug upon enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma 1/2 Life (t1/2)	plasma elimination 1/2 life (t1/2)	samples collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours after ingestion of study PPI drug
Weight-adjusted Clearance	Weight-adjusted Drug plasma clearance (CL/F)	samples collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours after ingestion of study PPI drug
AUC	Plasma Area Under the Curve	samples collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours after ingestion of study PPI drug
Hepatic Fat Fraction	Hepatic Fat Fraction as measured by liver Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)	MRI obtained anytime within 30 days of PK visit
Tmax	Time to max plasma concentration	samples collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours after ingestion of study PPI drug
Cmax	Weight-Adjusted maximum plasma concentration	samples collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours after ingestion of study PPI drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Cytokines	Mean and standard deviation of inflammatory cytokine levels measured from 58 of 71 participants who received pantoprazole. Cytokines include: INF-γ, IL-1β, IL-6.	Cytokines obtained from blood samples collected at pantoprazole PK study visit.

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Kathryn Kyler, MD, MS, Children's Mercy Hospital Kansas City

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Digestive System Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Overweight; Obesity; Esophageal Motility Disorders; Deglutition Disorders; Fatty Liver; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Non-alcoholic Fatty Liver Disease; Pediatric Obesity; Gastroesophageal Reflux; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Pantoprazole; Midazolam; Lansoprazole
• Other Study ID Numbers: STUDY00000201; K23DK115827-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified experimental data may be shared with institutional collaborators outside of CMH and if it is determined that biological samples obtained from study participants must be transferred to institutions outside of CMH for the purpose of confirmatory analyses, appropriate inter-institutional material transfer agreements will first be executed. As this is a pediatric study, minimal blood volumes are being collected and we do not anticipate that biological samples will be available to share with the outside community upon completion of the study, beyond those samples that may be required for confirmatory analyses.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No