Trial Outcomes & Findings for Effect of Obesity on Proton Pump Inhibitors (NCT NCT04248335)
NCT ID: NCT04248335
Last Updated: 2026-06-04
Results Overview
plasma elimination 1/2 life (t1/2)
COMPLETED
PHASE4
76 participants
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
2026-06-04
Participant Flow
Subjects were recruited from the Gastroenterology clinic at Children's Mercy Kansas City. Subjects were also recruited from a pool of previous research participants, in the Divisions of Gastroenterology, Hepatology and Nutrition or Clinical Pharmacology, Toxicology and Therapeutic Innovation (the PI's home divisions), who had opted in to be contacted for future research opportunities. A notice was also be publicly displayed in the waiting areas of outpatient clinics at CMH.
The study enrolled 76 participants to receive up to 3 drugs (lansoprazole n=48, pantoprazole n=71, midazolam n=29). Enrollment stopped prior to target enrollment completion for 1 drug (midazolam) as the original study PI left the institution. Some participants received ≥1 study drug: 13 received 1 study drug (either Lanso (5) or Panto (8), 54 received 2 drugs (Lanso+Panto (34) OR Panto+Midaz (20), and 9 received all 3 drugs. Those receiving lanso or panto returned for subsequent study visit.
Participant milestones
| Measure |
Participants Receiving Proton Pump Inhibitors
Children and young adults aged 6-21 years with and without obesity (based on CDC BMI definitions for age/sex) participated. Some participants received ≥1 study drug.
1. Lansoprazole -Participants were given a dose of oral lansoprazole dosed at 1.2 mg/kg fat free mass (FFM), with a maximum dose of 60mg. Then up to 12 blood samples were collected over the course of the 10 hours study visit. All urine voided during the PK study visit was collected.
2. Pantoprazole - Participants were given a dose (oral or IV) of pantoprazole dosed at 1.2 mg/kg fat free mass (FFM), with a maximum dose of 80mg. Then up to 12 blood samples were collected over the course of the 10 hours study visit. All urine voided during the PK study visit was collected.
3. Midazolam - To minimize discomfort of pH probe placement, participants in other arms were offered a one-time dose of IV midazolam (0.05mg/kg up to 2mg) to assist with probe placement. For those subjects who elected to have a one-time dose of IV midazolam, concentrations of midazolam and its relevant metabolites were measured in blood and urine samples that are already being collected for PPI PK analysis. An additional midazolam PK blood samples were drawn every 10-15 minutes after midazolam administration and before PPI dosing, during pH probe placement and calibration (approx. 30-45 min; up to 4 PK samples).
|
|---|---|
|
Overall Study
STARTED
|
76
|
|
Overall Study
Received Lansoprazole
|
48
|
|
Overall Study
Received Pantoprazole
|
71
|
|
Overall Study
Received Midazolam
|
29
|
|
Overall Study
COMPLETED
|
76
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Obesity on Proton Pump Inhibitors
Baseline characteristics by cohort
| Measure |
Participants Receiving PPI Study Drug(s)
n=76 Participants
76 participants enrolled to receive PPI study drug(s): 48 received lansoprazole (43 also received pantoprazole, 9 also received midazolam) 71 received pantoprazole (43 also received lansoprazole, 29 also received midazolam) 29 received midazolam (29 also received pantoprazole, and 9 also received lansoprazole)
|
|---|---|
|
Age, Categorical
<=18 years
|
69 Participants
n=9 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=9 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=9 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=9 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=9 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Black or African American
|
26 Participants
n=9 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=9 Participants
|
|
Race (NIH/OMB)
More than one race
|
7 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
|
CYP2C19 Phenotype
Poor metabolizer
|
2 Participants
n=9 Participants
|
|
CYP2C19 Phenotype
Intermediate metabolizer
|
21 Participants
n=9 Participants
|
|
CYP2C19 Phenotype
Normal metabolizer
|
25 Participants
n=9 Participants
|
|
CYP2C19 Phenotype
Rapid metabolizer
|
19 Participants
n=9 Participants
|
|
CYP2C19 Phenotype
Ultrarapid metabolizer
|
2 Participants
n=9 Participants
|
|
CYP2C19 Phenotype
Data Missing
|
7 Participants
n=9 Participants
|
|
Weight Category
No Obesity
|
35 Participants
n=9 Participants
|
|
Weight Category
Obesity
|
41 Participants
n=9 Participants
|
PRIMARY outcome
Timeframe: 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 drugPopulation: Noncompartmental analysis of lansoprazole included 41 participants at the time it was completed (when original PI left institution). Noncompartmental analysis of pantopraozle included 25 participants at the time it was completed (when original PI left institution). Noncompartmental pharmacokinetic analysis for midazolam was not started due to loss of personnel when original PI left institution. There is no future plan to analyze the data.
plasma elimination 1/2 life (t1/2)
Outcome measures
| Measure |
Lansoprazole
n=41 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
n=25 Participants
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
Plasma 1/2 Life (t1/2)
|
1.23 hours
Standard Deviation 0.77
|
1.09 hours
Standard Deviation 1.03
|
—
|
PRIMARY outcome
Timeframe: 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 drugPopulation: Noncompartmental analysis of lansoprazole included 41 participants at the time it was completed (when original PI left institution). Noncompartmental analysis of pantopraozle included 25 participants at the time it was completed (when original PI left institution). Noncompartmental pharmacokinetic analysis for midazolam was not started due to loss of personnel when original PI left institution. There is no future plan to analyze the data.
Weight-adjusted Drug plasma clearance (CL/F)
Outcome measures
| Measure |
Lansoprazole
n=41 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
n=25 Participants
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
Weight-adjusted Clearance
|
0.18 L//kg/hr
Standard Deviation 0.23
|
0.1 L//kg/hr
Standard Deviation 0.06
|
—
|
PRIMARY outcome
Timeframe: 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 drugPopulation: Noncompartmental analysis of lansoprazole included 41 participants at the time it was completed (when original PI left institution). Noncompartmental analysis of pantopraozle included 25 participants at the time it was completed (when original PI left institution). Noncompartmental pharmacokinetic analysis for midazolam was not started due to loss of personnel when original PI left institution. There is no future plan to analyze the data.
Plasma Area Under the Curve
Outcome measures
| Measure |
Lansoprazole
n=41 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
n=25 Participants
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
AUC
|
3.4 microgram/mL*h
Standard Deviation 3.5
|
6.5 microgram/mL*h
Standard Deviation 7.25
|
—
|
PRIMARY outcome
Timeframe: MRI obtained anytime within 30 days of PK visitPopulation: We have MRI data on 28 participants who received lansoprazole (not all had MRI performed). We have MRI data on 58 participants who received pantoprazole (not all had MRI performed). Midazolam HFF not available (analysis stopped due to loss of personnel when original PI left institution, some participants may have had MRI but HFF data is not available as calculations were not completed). There is no future plan to analyze the data.
Hepatic Fat Fraction as measured by liver Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)
Outcome measures
| Measure |
Lansoprazole
n=28 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
n=58 Participants
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
Hepatic Fat Fraction
|
2.82 Hepatic Fat Fraction %
Standard Deviation 6.78
|
3.0 Hepatic Fat Fraction %
Standard Deviation 13.6
|
—
|
PRIMARY outcome
Timeframe: 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 drugPopulation: Noncompartmental analysis of lansoprazole included 41 participants at the time it was completed (when original PI left institution). Noncompartmental analysis of pantopraozle included 25 participants at the time it was completed (when original PI left institution). Noncompartmental pharmacokinetic analysis for midazolam was not started due to loss of personnel when original PI left institution. There is no future plan to analyze the data.
Time to max plasma concentration
Outcome measures
| Measure |
Lansoprazole
n=41 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
n=25 Participants
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
Tmax
|
1.73 hours
Standard Deviation 1.14
|
2.5 hours
Standard Deviation 0.7
|
—
|
PRIMARY outcome
Timeframe: 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 drugPopulation: Noncompartmental analysis of lansoprazole included 41 participants at the time it was completed (when original PI left institution). Noncompartmental analysis of pantopraozle included 25 participants at the time it was completed (when original PI left institution). Noncompartmental pharmacokinetic analysis for midazolam was not started due to loss of personnel when original PI left institution. There is no future plan to analyze the data.
Weight-Adjusted maximum plasma concentration
Outcome measures
| Measure |
Lansoprazole
n=41 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
n=25 Participants
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
Cmax
|
2.49 microgram/mL/kg
Standard Deviation 1.72
|
4.95 microgram/mL/kg
Standard Deviation 2.83
|
—
|
SECONDARY outcome
Timeframe: Cytokines obtained from blood samples collected at pantoprazole PK study visit.Population: 13 of 71 pantoprazole participants missing cytokine data. Some additional participants had undetectable cytokine levels which are removed from the mean values calculated below. No participants who received lansoprazole had cytokine data, as this was added to the protocol after the study had completed lansoprazole enrollment - therefore, there is no lansoprazole arm listed for this outcome.
Mean and standard deviation of inflammatory cytokine levels measured from 58 of 71 participants who received pantoprazole. Cytokines include: INF-γ, IL-1β, IL-6.
Outcome measures
| Measure |
Lansoprazole
n=58 Participants
Children enrolled who received lansoprazole.
|
Pantoprazole
Children enrolled who received pantoprazole.
|
Midazolam
Children enrolled who received midazolam.
|
|---|---|---|---|
|
Inflammatory Cytokines
INF-γ levels
|
12.1 ng/L
Standard Deviation 36.8
|
—
|
—
|
|
Inflammatory Cytokines
IL-1β levels
|
1.07 ng/L
Standard Deviation 1.91
|
—
|
—
|
|
Inflammatory Cytokines
IL-6 levels
|
10.7 ng/L
Standard Deviation 29.55
|
—
|
—
|
Adverse Events
Lansoprazole
Pantoprazole
Midazolam
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place