Effect of Obesity on Proton Pump Inhibitors

NCT ID: NCT04248335

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-03
• Study Completion Date: 2024-12-31

Brief Summary

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

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.

Conditions

Pediatric Obesity; NAFLD; GERD

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

In Weight Management Program

Evaluate the effect of liver fat on pharmacology of PPI's, and if applicable midazolam

Group Type: EXPERIMENTAL

Pantoprazole

Intervention Type: DRUG

single-dose administration

Midazolam injection

Intervention Type: DRUG

single-dose administration

Not in Weight Management Program

Evaluate the effect of liver fat on drug metabolism of PPI's, and if applicable midazolam

Group Type: EXPERIMENTAL

Pantoprazole

Intervention Type: DRUG

single-dose administration

Midazolam injection

Intervention Type: DRUG

single-dose administration

Interventions

Pantoprazole

single-dose administration

Intervention Type: DRUG

Midazolam injection

single-dose administration

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Kate Kyler, MD, MSc

Physician Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kathryn Kyler, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hospital Kansas City

Locations

Children's Mercy Kansas City

Kansas City, Missouri, United States

Countries

United States

Other Identifiers

K23DK115827-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00000201

Identifier Type: -

Identifier Source: org_study_id