Clinical trial NCT04248335: Effect of Obesity on Proton Pump Inhibitors
Official title: Physiologic Determinants of PPI Disposition in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pediatric Obesity
NAFLD
GERD
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-01-30
Enrollment: 150
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: plasma pharmacokinetics of pantoprazole
timeFrame: 5 years
measure: plasma pharmacokinetics of pantoprazole
timeFrame: 5 years
measure: plasma pharmacokinetics of pantoprazole
timeFrame: 5 years
measure: plasma pharmacokinetics of pantoprazole
timeFrame: 5 years
measure: plasma pharmacokinetics of pantoprazole
timeFrame: 5 years
measure: plasma pharmacokinetics of pantoprazole
timeFrame: 5 years
Secondary outcomes:
measure: pharmacodynamics
timeFrame: 5 years
measure: safety of pantoprazole: incidence of reported and gastrointestinal adverse events
timeFrame: 5 years
measure: pharmacokinetics of midazolam, if medication received to ease discomfort of pH probe study
timeFrame: 5 years
measure: urinary metabolites
timeFrame: 5 years
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Missouri
Study officials:
affiliation: Children's Mercy Hospital Kansas City
name: Kathryn Kyler, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: