Effect of Obesity on Proton Pump Inhibitors

NAFLD Clinical Trial

— LiverLabPPI  

Official title:

Physiologic Determinants of PPI Disposition in Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04248335
• Other study ID #: STUDY00000201
• Status: Recruiting
• Phase: Phase 4
• Start date: July 3, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Children's Mercy Hospital Kansas City
• Contact: Simone Lax
• Phone: (816) 394-7542
• Email: snlax[@]cmh.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

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)

Related Conditions & MeSH terms

• GERD
• NAFLD
• Obesity
• Pediatric Obesity

Intervention

Drug:
• Pantoprazole
single-dose administration
• Midazolam injection
single-dose administration

Locations

Country	Name	City	State
United States	Children's Mercy Kansas City	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Children's Mercy Hospital Kansas City

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma pharmacokinetics of pantoprazole	plasma maximum peak concentration (Cmax)	5 years
Primary	plasma pharmacokinetics of pantoprazole	area under the concentration time curve (AUC)	5 years
Primary	plasma pharmacokinetics of pantoprazole	time to maximum peak concentration (tmax)	5 years
Primary	plasma pharmacokinetics of pantoprazole	half-life (t 1/2)	5 years
Primary	plasma pharmacokinetics of pantoprazole	volume of distribution (Vd)	5 years
Primary	plasma pharmacokinetics of pantoprazole	clearance (CL)	5 years
Secondary	pharmacodynamics	concentration of gastric acid using pH probe test	5 years
Secondary	safety of pantoprazole: incidence of reported and gastrointestinal adverse events	incidence of reported and gastrointestinal adverse events	5 years
Secondary	pharmacokinetics of midazolam, if medication received to ease discomfort of pH probe study	plasma concentrations of midazolam	5 years
Secondary	urinary metabolites	urine concentrations of pantoprazole and midazolam and their metabolites	5 years