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Effect of Obesity on Proton Pump Inhibitors (LiverLabPPI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04248335
Recruitment Status : Suspended (Suspended due to COVID-19; No suspension of IRB approval)
First Posted : January 30, 2020
Last Update Posted : May 22, 2020
Sponsor:
Information provided by (Responsible Party):
Valentina Shakhnovich, Children's Mercy Hospital Kansas City

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

Condition or disease Intervention/treatment Phase
Pediatric Obesity NAFLD GERD Drug: Pantoprazole Drug: Midazolam injection Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Physiologic Determinants of PPI Disposition in Children
Actual Study Start Date : January 27, 2020
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: In Weight Management Program
Evaluate the effect of liver fat on pharmacology of PPI's, and if applicable midazolam
Drug: Pantoprazole
single-dose administration

Drug: Midazolam injection
single-dose administration

Experimental: Not in Weight Management Program
Evaluate the effect of liver fat on drug metabolism of PPI's, and if applicable midazolam
Drug: Pantoprazole
single-dose administration

Drug: Midazolam injection
single-dose administration




Primary Outcome Measures :
  1. plasma pharmacokinetics of pantoprazole [ Time Frame: 5 years ]
    plasma maximum peak concentration (Cmax)

  2. plasma pharmacokinetics of pantoprazole [ Time Frame: 5 years ]
    area under the concentration time curve (AUC)

  3. plasma pharmacokinetics of pantoprazole [ Time Frame: 5 years ]
    time to maximum peak concentration (tmax)

  4. plasma pharmacokinetics of pantoprazole [ Time Frame: 5 years ]
    half-life (t 1/2)

  5. plasma pharmacokinetics of pantoprazole [ Time Frame: 5 years ]
    volume of distribution (Vd)

  6. plasma pharmacokinetics of pantoprazole [ Time Frame: 5 years ]
    clearance (CL)


Secondary Outcome Measures :
  1. pharmacodynamics [ Time Frame: 5 years ]
    concentration of gastric acid using pH probe test

  2. safety of pantoprazole: incidence of reported and gastrointestinal adverse events [ Time Frame: 5 years ]
    incidence of reported and gastrointestinal adverse events

  3. pharmacokinetics of midazolam, if medication received to ease discomfort of pH probe study [ Time Frame: 5 years ]
    plasma concentrations of midazolam

  4. urinary metabolites [ Time Frame: 5 years ]
    urine concentrations of pantoprazole and midazolam and their metabolites



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 ≥ 3 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04248335


Locations
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United States, Missouri
Children's Mercy Kansas City
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Investigators
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Principal Investigator: Valentina Shakhnovich, MD Children's Mercy Hospital Kansas City
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Responsible Party: Valentina Shakhnovich, Physician Scientist, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT04248335    
Other Study ID Numbers: STUDY00000201
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Deidentified experimental data may be shared with institutional collaborators outside of CMH and if it is determined that biological samples obtained from study participants must be transferred to institutions outside of CMH for the purpose of confirmatory analyses, appropriate inter-institutional material transfer agreements will first be executed. As this is a pediatric study, minimal blood volumes are being collected and we do not anticipate that biological samples will be available to share with the outside community upon completion of the study, beyond those samples that may be required for confirmatory analyses.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Obesity
Pediatric Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Midazolam
Pantoprazole
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors