Effect of Obesity on Proton Pump Inhibitors

NCT04248335 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: STUDY00000201K23DK115827-01A1
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

NAFLD; GERD; Pediatric Obesity

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Inflammatory Cytokines

  Cytokines obtained from blood samples collected at pantoprazole PK study visit.

Study Arms (1)

Children enrolled to receive proton pump inhibitor

EXPERIMENTAL

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

Drug: Lansoprazole; Drug: Pantoprazole; Drug: Midazolam

Interventions

Pantoprazole DRUG

single-dose administration. Administered to a subset of participants who agreed to receive this drug upon enrollment.

Children enrolled to receive proton pump inhibitor

Lansoprazole DRUG

single-dose administration. Administered to a subset of participants who agreed to receive this drug upon enrollment.

Children enrolled to receive proton pump inhibitor

Midazolam DRUG

single-dose administration. Administered to a subset of participants who agreed to receive this drug upon enrollment.

Children enrolled to receive proton pump inhibitor

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Children's Mercy Kansas City

Kansas City, Missouri, 64108, United States

Location

MeSH Terms

Conditions

Pediatric Obesity; Non-alcoholic Fatty Liver Disease; Gastroesophageal Reflux

Interventions

Lansoprazole; Pantoprazole; Midazolam

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines

Limitations and Caveats

Although our population model is based on a relatively small sample size (n=40), it is the only published model of PPI PK for obese children. Model-derived PK parameters were substantially different from those previously reported for non-obese children, who were not included in this study, as the study objective was to describe pantoprazole PK specifically for obese children.

Results Point of Contact

• Title: Kathryn Kyler
• Organization: Children's Mercy Kansas City

kekyler@cmh.edu

816-302-3266

Study Officials

• Kathryn Kyler, MD, MS

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Scientist

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 30, 2020
• Study Start: July 3, 2018
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 4, 2026
• Results First Posted: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)