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| Name | Class |
|---|---|
| AbbVie | INDUSTRY |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Phoenix Indian Medical Center | UNKNOWN |
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The objective of this study is to evaluate the malabsorption blood test (MBT), stool coefficient of fat absorption (CFA) and stool bomb calorimetry (BC) methods as potential screening or diagnostic tests for reduced exocrine pancreatic function or pancreatic insufficiency (RPF/PI). A further objective is to determine the test responses before and after pancreatic enzyme medication administration (Creon36™) in the patients with chronic pancreatitis (CP).
Reduced exocrine pancreatic function or pancreatic insufficiency (RPF/PI) contributes to poor clinical outcome in a number of diseases and conditions. The incidence, mechanism and substantial adverse clinical outcomes of pancreatic insufficiency (PI) are well known in patients with cystic fibrosis (CF), and the life sustaining role of pancreatic enzyme medication in CF care is well established. Much less is known about the incidence and impact of RPF/PI in patients with chronic pancreatitis (CP). Reliable non-invasive screening or diagnostic tests with acceptable patient burden are not available for RPF/PI.
This is a cohort study of subjects with CP who will be evaluated before and after pancreatic enzyme medication (Creon36™) administration. A cohort of healthy subjects will serve as a comparison group and will be evaluated only once.
Subjects with CP will receive Creon36™, a pancreatic enzyme medication, and fat and energy absorption will be evaluated using three methods: MBT, CFA, and BC before and after administration of Creon36™. Many patients with CP are at risk for RPF/PI yet they rarely undergo diagnostic testing. Pancreatic enzyme medication will likely improve clinical outcomes and quality of life in some of those with RPF/PI. A cohort of healthy volunteers will be evaluated with the three methods to provide essential comparison data to optimize the understanding and interpretation of the findings from the three methods and the RPF/PI cohort with CP. There will be no intervention for the healthy cohort.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic Pancreatitis (CP) Subjects | Experimental | CP subjects will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. Subjects will take Creon36™ for 9 days. Subjects will have two study visits, one before and one after treatment initiation with Creon36™. Both visits will be identical with the exception of completion of questionnaires and fecal elastase assessment (only Visit 1). |
|
| Healthy Controls | No Intervention | Healthy controls will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. Controls will only have 1 study visit and receive no intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Creon36™ | Drug | Creon36™ delayed-release capsules, a pancreatic enzyme preparation, is an FDA approved medication. Subjects with chronic pancreatitis (CP) will take Creon36™ for nine days, at a daily dose of 72,000 lipase units per meal (two capsules) and 36,000 units per snack (one capsule), with each capsule containing 36,000 lipase units. Subjects will take Creon36™ for three days prior to Visit 2, the day of Visit 2 and then for five days after the visit until they have completed stool collections. |
| Measure | Description | Time Frame |
|---|---|---|
| Malabsorption Blood Test: Difference in Mean HA AUC Between Groups: Subjects With CP Compared to Healthy Subjects | The fat absorption pattern in CP subjects will be compared with healthy controls. Mean HA AUC will be calculated for the CP subjects and the healthy controls and compared to determine whether there is a difference in the fat absorption between the two groups. | 8 hours |
| Coefficient of Fat Absorption: Difference in Mean % Dietary Fat Absorption Between Groups: Subjects With CP Compared to Healthy Subjects | The fat absorption pattern in CP subjects will be compared with healthy controls. Mean coefficient of fat absorption (% dietary fat absorbed) will be calculated for the CP subjects and the healthy controls and compared to determine whether there is a difference in the fat absorption between the two groups. | 72 hours |
| Bomb Calorimetry: Difference in Mean Stool Energy Loss Between Groups: Subjects With CP Compared to Healthy Subjects | The energy absorption pattern in CP subjects will be compared with healthy controls. Mean calories per gram of stool will be calculated for the CP subjects and the healthy controls and compared to determine whether there is a difference in the stool energy loss between the two groups. | 72 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Bomb Calorimetry: Difference in Mean Energy Loss Between Groups: Subjects With CP Before and After Creon36™ | The energy absorption pattern in CP subjects before and after treatment with Creon36™ will be compared. Calories per gram of stool will be calculated for the CP subjects before and after the medication and compared to determine whether there is a difference in the stool energy loss in the same subjects between the two time points. |
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Inclusion Criteria (CP):
Inclusion Criteria (Healthy Volunteers):
Exclusion Criteria (CP):
Exclusion Criteria (Healthy Volunteers):
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| Name | Affiliation | Role |
|---|---|---|
| Babette Zemel, PhD | Children's Hospital of Philadelphia | Principal Investigator |
| Virginia Stallings, MD | Children's Hospital of Philadelphia | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
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There were no events between enrollment and assignment in either group. All subjects enrolled were assigned to the appropriate arm.
Subjects were recruited from academic medical centers in the Philadelphia region between August 2016 and November 2017. For the CP cohort, subjects were diagnosed with CP by a gastroenterologist based on criteria as recommended by the American Pancreatic Association (APA) Practice Guidelines.
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| ID | Title | Description |
|---|---|---|
| FG000 | Chronic Pancreatitis (CP) Subjects | CP subjects will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. This visit will be repeated after initiation of Creon36™. |
| FG001 | Healthy Controls | Healthy controls will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. Controls will only have 1 study visit and receive no intervention. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Washout Period - CP Subj on PERT - 3days |
| |||||||||||||
| Baseline Assessments - All Subj - 7 Days |
| |||||||||||||
| Assessment on PERT - CP Subj - 16 Days |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Chronic Pancreatitis (CP) Subjects | CP subjects will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. This visit will be repeated after initiation of Creon36™. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Two healthy subjects were found after completion of assessments to have chronic illnesses not initially disclosed upon enrollment. Since they did not meet original inclusion criteria, they were dropped from analysis. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Malabsorption Blood Test: Difference in Mean HA AUC Between Groups: Subjects With CP Compared to Healthy Subjects | The fat absorption pattern in CP subjects will be compared with healthy controls. Mean HA AUC will be calculated for the CP subjects and the healthy controls and compared to determine whether there is a difference in the fat absorption between the two groups. | Two subjects with CP were excluded; one did not complete the study meal for a valid test, and one was a significant outlier calling into question the validity of the test. Of the 24 healthy controls, two were excluded from the study due to undisclosed chronic disease, and two subjects did not complete the study meal for a valid test. | Posted | Mean | Standard Deviation | mg*h/dL | 8 hours |
|
Adverse events were collected for the time period during which study procedures were undertaken. For healthy subjects, this includes the 7 days surrounding the assessment visit. For subjects with CP, this includes the 7 days surrounding the baseline assessment visit and the 9 days during which the subjects took Creon surrounding the second assessment visit.
Adverse events were collected by personal interview during the visit itself, and by phone call after the completion of study procedures.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chronic Pancreatitis (CP) Subjects | CP subjects will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. This visit will be repeated after initiation of Creon36™. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain/Discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Virginia Stallings, MD | Children's Hospital of Philadelphia | 267.425.1633 | stallingsv@email.chop.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 5, 2017 | Feb 26, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D050500 | Pancreatitis, Chronic |
| D010188 | Exocrine Pancreatic Insufficiency |
| ID | Term |
|---|---|
| D010195 | Pancreatitis |
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D020799 | Pancrelipase |
| ID | Term |
|---|---|
| D008049 | Lipase |
| D002265 | Carboxylic Ester Hydrolases |
| D004950 | Esterases |
| D006867 | Hydrolases |
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|
|
| 72 hours |
| Malabsorption Blood Test: Difference in Mean HA AUC Between Groups: Subjects With CP Before and After Creon36™ | The fat absorption pattern in CP subjects before and after treatment with Creon36™ will be compared. Mean HA AUC will be calculated for the CP subjects before and after the medication and compared to determine whether there is a difference in the fat absorption in the same subjects between the two time points. | 8 hours |
| Coefficient of Fat Absorption: Difference in Mean % Dietary Fat Absorption Between Groups: Subjects With CP Before and After Creon36™ | The fat absorption pattern in CP subjects before and after treatment with Creon36™ will be compared. The % of dietary fat absorbed will be calculated for the CP subjects before and after the medication and compared to determine whether there is a difference in the fat absorption in the same subjects between the two time points. | 72 hours |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
|
| BG001 | Healthy Controls | Healthy controls will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. Controls will only have 1 study visit and receive no intervention. |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Two healthy subjects were found after completion of assessments to have chronic illnesses not initially disclosed upon enrollment. Since they did not meet original inclusion criteria, they were dropped from analysis. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Two healthy subjects were found after completion of assessments to have chronic illnesses not initially disclosed upon enrollment. Since they did not meet original inclusion criteria, they were dropped from analysis. | Count of Participants | Participants |
|
| Race (NIH/OMB) | Two healthy subjects were found after completion of assessments to have chronic illnesses not initially disclosed upon enrollment. Since they did not meet original inclusion criteria, they were dropped from analysis. | Count of Participants | Participants |
|
| BMI | Body Mass Index | Two healthy subjects were found after completion of assessments to have chronic illnesses not initially disclosed upon enrollment. Since they did not meet original inclusion criteria, they were dropped from analysis. | Mean | Standard Deviation | kg/m^2 |
|
| Fecal Elastase | This measure was only baseline for the CP group. | Mean | Standard Deviation | ug/g stool |
|
| Coefficient of Fat Absorption | Two healthy subjects were found after completion of assessments to have chronic illnesses not initially disclosed upon enrollment. Since they did not meet original inclusion criteria, they were dropped from analysis. Four subjects with CP did not have adequate stool collection (n=2) or fat intake (n=2) for a valid CFA test. | Mean | Standard Deviation | % of dietary fat absorbed |
|
| Bomb Calorimetry | 2 healthy subjects were found after assessment to have chronic illnesses not initially disclosed; they were dropped from analysis. 3 subjects were excluded from analysis due to uncertainty in test result (high variability in test runs). 1 subject with CP was excluded due to uncertainty, 2 were excluded due to inadequate stool collection. | Mean | Standard Deviation | cal/g stool |
|
| HA AUC | Area under the curve for heptadecanoic acid | Of the subjects with CP, one did not complete the study meal for a valid test, and one was a significant outlier. Of the healthy subjects, two were deemed not healthy as previously explained, and two did not complete the study meal for a valid test. | Mean | Standard Deviation | mg*h/dL |
|
| OG001 | Healthy Controls | Healthy controls will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. Controls will only have 1 study visit and receive no intervention. |
|
|
|
| Primary | Coefficient of Fat Absorption: Difference in Mean % Dietary Fat Absorption Between Groups: Subjects With CP Compared to Healthy Subjects | The fat absorption pattern in CP subjects will be compared with healthy controls. Mean coefficient of fat absorption (% dietary fat absorbed) will be calculated for the CP subjects and the healthy controls and compared to determine whether there is a difference in the fat absorption between the two groups. | Four subjects with CP were excluded; two did not consume enough fat for a valid test, one subject did not have adequate stool for analysis, and one subject was excluded due to an error in the lab processing stool. Of the 24 healthy controls, two were excluded from the analysis due to undisclosed chronic disease. | Posted | Mean | Standard Deviation | % of dietary fat intake | 72 hours |
|
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|
|
| Primary | Bomb Calorimetry: Difference in Mean Stool Energy Loss Between Groups: Subjects With CP Compared to Healthy Subjects | The energy absorption pattern in CP subjects will be compared with healthy controls. Mean calories per gram of stool will be calculated for the CP subjects and the healthy controls and compared to determine whether there is a difference in the stool energy loss between the two groups. | Three subjects with CP were excluded; two did not consume enough fat for a valid test, one subject did not have adequate stool for analysis. Of the 24 healthy controls, two were excluded from the analysis due to undisclosed chronic disease, one did not provide adequate stool for analysis, and two results failed internal the validation protocol. | Posted | Mean | Standard Deviation | calories/gram of stool | 72 hours |
|
|
|
|
| Secondary | Bomb Calorimetry: Difference in Mean Energy Loss Between Groups: Subjects With CP Before and After Creon36™ | The energy absorption pattern in CP subjects before and after treatment with Creon36™ will be compared. Calories per gram of stool will be calculated for the CP subjects before and after the medication and compared to determine whether there is a difference in the stool energy loss in the same subjects between the two time points. | Two subjects were excluded from follow-up due to inadequate stool provision. Two subjects were excluded due to failing the internal validation protocol. | Posted | Mean | Standard Deviation | calories/gram of stool | 72 hours |
|
|
|
|
| Secondary | Malabsorption Blood Test: Difference in Mean HA AUC Between Groups: Subjects With CP Before and After Creon36™ | The fat absorption pattern in CP subjects before and after treatment with Creon36™ will be compared. Mean HA AUC will be calculated for the CP subjects before and after the medication and compared to determine whether there is a difference in the fat absorption in the same subjects between the two time points. | For this paired analysis, twenty subjects had valid tests at both time points. Two subjects were excluded from baseline; one did not complete the study meal for a valid test, and one was a significant outlier calling into question the validity of the test. Two subjects were excluded from follow-up, as they did not complete the study meal or test. | Posted | Mean | Standard Deviation | mg*h/dL | 8 hours |
|
|
|
|
| Secondary | Coefficient of Fat Absorption: Difference in Mean % Dietary Fat Absorption Between Groups: Subjects With CP Before and After Creon36™ | The fat absorption pattern in CP subjects before and after treatment with Creon36™ will be compared. The % of dietary fat absorbed will be calculated for the CP subjects before and after the medication and compared to determine whether there is a difference in the fat absorption in the same subjects between the two time points. | Two subjects were excluded from baseline due to inadequate dietary fat intake for a valid test, and one was excluded for inadequate stool provision. Three subjects were excluded at follow up for inadequate dietary information and stool provision. One subject was excluded from follow up due to lab error. | Posted | Mean | Standard Deviation | % of dietary fat intake | 72 hours |
|
|
|
|
| 0 |
| 24 |
| 0 |
| 24 |
| 7 |
| 24 |
| EG001 | Healthy Controls | Healthy controls will fast for 12 hours prior to the malabsorption blood test (MBT) testing, consume the MBT breakfast meal following this fast, have blood drawn (MBT, vitamins A, D, E and K, zinc, selenium, and prealbumin) prior to MBT breakfast consumption and each hour for 8 hours after consumption, consume a low-fat study lunch, eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, collect stool over 72 hours, have body size and composition assessment, complete quality of life questionnaires, home environment and health questionnaires, and adverse events diary. Controls will only have 1 study visit and receive no intervention. | 0 | 24 | 0 | 24 | 3 | 24 |
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| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D010184 | Pancreatic Extracts |
| D014020 | Tissue Extracts |
| D045424 | Complex Mixtures |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|