Effect of Obesity on Proton Pump Inhibitors

NCT04248335 | Completed Phase 4 FDA Drug

• 2 other identifiers: STUDY00000201K23DK115827-01A1
• Study Type: interventional
• Target: 150
• 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

Pediatric Obesity; NAFLD; GERD

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• pharmacodynamics

  5 years

• safety of pantoprazole: incidence of reported and gastrointestinal adverse events

  5 years

• pharmacokinetics of midazolam, if medication received to ease discomfort of pH probe study

  5 years

• urinary metabolites

  5 years

Study Arms (2)

In Weight Management Program

EXPERIMENTAL

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

Drug: Pantoprazole; Drug: Midazolam injection

Not in Weight Management Program

EXPERIMENTAL

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

Drug: Pantoprazole; Drug: Midazolam injection

Interventions

Pantoprazole DRUG

single-dose administration

In Weight Management Program; Not in Weight Management Program

Midazolam injection DRUG

single-dose administration

In Weight Management Program; Not in Weight Management Program

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

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

Study Officials

• Kathryn Kyler, MD, MS

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• 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: January 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)