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: Recruiting
• Conditions: Pediatric Obesity; GERD; NAFLD
• Intervention / Treatment: Drug: Pantoprazole; Drug: Midazolam injection

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 (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jaylene D Weigel; Phone Number: 8167011359; Email: jaydweigel@gmail.com
• Study Contact Backup: Name: Simone Lax; Phone Number: (816) 394-7542; Email: snlax@cmh.edu

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy Kansas City
      • Contact: Jaylene D Weigel; Phone Number: 8167011359; Email: jweigel@cmh.edu
      • Contact: Simone Lax; Phone Number: 816-394-7542; Email: snlax@cmh.edu

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: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: In Weight Management Program; Evaluate the effect of liver fat on pharmacology of PPI's, and if applicable midazolam	Drug: Pantoprazole; single-dose administration; Drug: Midazolam injection; single-dose administration
Experimental: Not in Weight Management Program; Evaluate the effect of liver fat on drug metabolism of PPI's, and if applicable midazolam	Drug: Pantoprazole; single-dose administration; Drug: Midazolam injection; single-dose administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma pharmacokinetics of pantoprazole	plasma maximum peak concentration (Cmax)	5 years
plasma pharmacokinetics of pantoprazole	area under the concentration time curve (AUC)	5 years
plasma pharmacokinetics of pantoprazole	time to maximum peak concentration (tmax)	5 years
plasma pharmacokinetics of pantoprazole	half-life (t 1/2)	5 years
plasma pharmacokinetics of pantoprazole	volume of distribution (Vd)	5 years
plasma pharmacokinetics of pantoprazole	clearance (CL)	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacodynamics	concentration of gastric acid using pH probe test	5 years
safety of pantoprazole: incidence of reported and gastrointestinal adverse events	incidence of reported and gastrointestinal adverse events	5 years
pharmacokinetics of midazolam, if medication received to ease discomfort of pH probe study	plasma concentrations of midazolam	5 years
urinary metabolites	urine concentrations of pantoprazole and midazolam and their metabolites	5 years

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City
• 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 (Estimated): December 31, 2024
• Study Completion (Estimated): 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): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Midazolam; Pantoprazole
• Other Study ID Numbers: STUDY00000201

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