Pancreatic Insufficiency, Cystic Fibrosis
Conditions
Keywords
fat absorption, pancreatic enzyme
Brief summary
This is a clinical trial with a cross over design investigating the effect of the proton pump inhibitor omeprazole on fat malabsorption in subjects with cystic fibrosis and pancreatic insufficiency. Participants will be randomized to receive either omeprazole or placebo for 28 days, then cross over and receive omeprazole or placebo for another 28 days. Markers of fat absorption will be measured after each treatment course.
Detailed description
Fat malabsorption contributes to poor nutritional status in people with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve PERT efficacy and dietary fat absorption has become accepted clinical practice in CF, despite limited evidence to support the practice. Establishing the efficacy and true health benefit of acid suppression for nutritional status and outcomes in CF is particularly important in light of potential health risks and cost associated with long-term or even lifetime use of these medications. This study aims to characterize changes in fat malabsorption using the coefficient of fat absorption (CFA) as the primary endpoint in subjects who are on and off acid suppression with a PPI in addition to PERT. Additionally, the SmartPill® will be used to evaluate duodenal power of hydrogen (pH) while on and off acid suppression, and the malabsorption blood test (MBT) will be used to characterize changes in fat absorption. Associations will be explored between changes in nutritional status (weight, height, BMI), clinical GI symptoms, and quality of life in subjects treated with PPI vs. placebo.
Interventions
Omeprazole 20mg daily for 28 days
DRUGPlacebo oral capsule
Identically-appearing capsule to omeprazole for 28 days
Sponsors
Chiesi USA, Inc.
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cystic fibrosis and pancreatic insufficiency (Fecal elastase \<200 ug/g stool) * Age ≥12 years * In usual state of good health * Willing to participate in a four-month study with three visits
Exclusion criteria
* Forced expiratory vital capacity at one second (FEV1) \<40% predicted * Pregnancy or breast feeding * Other illness affecting growth or nutritional status * Unwillingness to continue their clinically established PERT dose for the duration of the study * Use of other medication that affects dietary fat absorption * Allergy to soy products * Allergy to safflower products * For subjects ≥18 years, celiac disease or allergy to gluten
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coefficient of Fat Absorption | After 28 days of treatment or placebo | Gold standard measurement of fat malabsorption |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duodenal pH | After 28 days of treatment or placebo | Change in duodenal pH as measured by the motility testing system (SmartPill) |
| Fat Absorption Via Malabsorption Blood Test | After 28 days of treatment or placebo | Measurement of serum pentadecanoic acid and heptadecanoic acid |
Countries
United States
Participant flow
Recruitment details
This is a randomized, cross-over study for which 19 participants were consented/enrolled; not all participants initiated study drug/placebo. Participants were randomized to receive placebo or drug first.
Pre-assignment details
19 subjects were randomized. There were 13 evaluable subjects who completed data collection at the end of the treatment period and 6 subjects did not complete data collection.
Participants by arm
| Arm | Count |
|---|---|
| Study Drug First, Then Placebo Subjects will take omeprazole 20mg daily for 28 days, then undergo assessments of fat absorption.
Omeprazole 20mg Capsule: Omeprazole 20mg daily for 28 days | 6 |
| Placebo First, Then Study Drug Subjects will take a placebo daily for 28 days, then undergo assessments of fat absorption.
Placebo oral capsule: Identically-appearing capsule to omeprazole for 28 days | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Study Drug First, Then Placebo | Placebo First, Then Study Drug | Total |
|---|---|---|---|
| Age, Continuous | 19 years STANDARD_DEVIATION 4 | 19 years STANDARD_DEVIATION 4 | 19 years STANDARD_DEVIATION 4 |
| Race/Ethnicity, Customized African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Coefficient of Fat Absorption
Gold standard measurement of fat malabsorption
Time frame: After 28 days of treatment or placebo
Population: The primary outcome measurement (CFA) was not available for 2 participants who got study drug first and 2 participants who got placebo first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omeprazole | Coefficient of Fat Absorption | 80 % fat absorption | Standard Deviation 20 |
| Placebo | Coefficient of Fat Absorption | 77 % fat absorption | Standard Deviation 16 |
Secondary
Duodenal pH
Change in duodenal pH as measured by the motility testing system (SmartPill)
Time frame: After 28 days of treatment or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omeprazole | Duodenal pH | 6.03 pH | Standard Deviation 0.4 |
| Placebo | Duodenal pH | 5.38 pH | Standard Deviation 0.8 |
Secondary
Fat Absorption Via Malabsorption Blood Test
Measurement of serum pentadecanoic acid and heptadecanoic acid
Time frame: After 28 days of treatment or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omeprazole | Fat Absorption Via Malabsorption Blood Test | 7.3 mg*h/dl | Standard Deviation 2.1 |
| Placebo | Fat Absorption Via Malabsorption Blood Test | 9.6 mg*h/dl | Standard Deviation 3.4 |