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Fat Malabsorption in Chronic Pancreatitis

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ClinicalTrials.gov Identifier: NCT02849704
Recruitment Status : Completed
First Posted : July 29, 2016
Results First Posted : May 3, 2019
Last Update Posted : May 3, 2019
Sponsor:
Collaborators:
AbbVie
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phoenix Indian Medical Center
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Condition Chronic Pancreatitis
Intervention Drug: Creon36™
Enrollment 48
Recruitment Details 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.
Pre-assignment Details There were no events between enrollment and assignment in either group. All subjects enrolled were assigned to the appropriate arm.
Arm/Group Title Chronic Pancreatitis (CP) Subjects Healthy Controls
Hide Arm/Group Description 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™. 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.
Period Title: Washout Period - CP Subj on PERT - 3days
Started [1] 11 0
Completed 11 0
Not Completed 0 0
[1]
Subjects with a diagnosis of CP and who were taking PERT participated in this Period
Period Title: Baseline Assessments - All Subj - 7 Days
Started 24 24
Completed 24 24
Not Completed 0 0
Period Title: Assessment on PERT - CP Subj - 16 Days
Started 24 0
Completed 21 0
Not Completed 3 0
Reason Not Completed
Lost to Follow-up             1             0
Adverse Event             1             0
Unable to complete study procedures             1             0
Arm/Group Title Chronic Pancreatitis (CP) Subjects Healthy Controls Total
Hide Arm/Group Description 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™. 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. Total of all reporting groups
Overall Number of Baseline Participants 24 24 48
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 22 participants 46 participants
50.7  (9.6) 43.4  (10) 47.1  (10.4)
[1]
Measure Analysis Population Description: 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.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Female
11
  45.8%
15
  68.2%
26
  56.5%
Male
13
  54.2%
7
  31.8%
20
  43.5%
[1]
Measure Analysis Population Description: 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.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Hispanic or Latino
1
   4.2%
1
   4.5%
2
   4.3%
Not Hispanic or Latino
23
  95.8%
21
  95.5%
44
  95.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: 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.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   8.3%
1
   4.5%
3
   6.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  37.5%
9
  40.9%
18
  39.1%
White
13
  54.2%
12
  54.5%
25
  54.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: 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.
BMI   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 24 participants 22 participants 46 participants
23.9  (3.6) 25.6  (4.4) 24.7  (4.0)
[1]
Measure Description: Body Mass Index
[2]
Measure Analysis Population Description: 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.
Fecal Elastase   [1] 
Mean (Standard Deviation)
Unit of measure:  Ug/g stool
Number Analyzed 24 participants 0 participants 24 participants
169  (172) 169  (172)
[1]
Measure Analysis Population Description: This measure was only baseline for the CP group.
Coefficient of Fat Absorption   [1] 
Mean (Standard Deviation)
Unit of measure:  % of dietary fat absorbed
Number Analyzed 20 participants 22 participants 42 participants
90.9  (12.8) 95.4  (9.3) 93.2  (9.2)
[1]
Measure Analysis Population Description:

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.

Bomb Calorimetry   [1] 
Mean (Standard Deviation)
Unit of measure:  Cal/g stool
Number Analyzed 21 participants 19 participants 40 participants
5728  (717) 5171  (393) 5463  (635)
[1]
Measure Analysis Population Description: 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.
HA AUC   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg*h/dL
Number Analyzed 22 participants 20 participants 42 participants
8.3  (4.3) 17.7  (10.3) 12.7  (9.1)
[1]
Measure Description: Area under the curve for heptadecanoic acid
[2]
Measure Analysis Population Description: 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.
1.Primary Outcome
Title Malabsorption Blood Test: Difference in Mean HA AUC Between Groups: Subjects With CP Compared to Healthy Subjects
Hide Description 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.
Time Frame 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Chronic Pancreatitis (CP) Subjects Healthy Controls
Hide Arm/Group Description:
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™.
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.
Overall Number of Participants Analyzed 22 20
Mean (Standard Deviation)
Unit of Measure: mg*h/dL
8.3  (4.3) 17.7  (10.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronic Pancreatitis (CP) Subjects, Healthy Controls
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments a priori threshold for significance: <0.05
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Coefficient of Fat Absorption: Difference in Mean % Dietary Fat Absorption Between Groups: Subjects With CP Compared to Healthy Subjects
Hide Description 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.
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Chronic Pancreatitis (CP) Subjects Healthy Controls
Hide Arm/Group Description:
As part of the primary assessment, CP subjects will eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, and collect stool over 72 hours.
Healthy controls will eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, and collect stool over 72 hours.
Overall Number of Participants Analyzed 20 22
Mean (Standard Deviation)
Unit of Measure: % of dietary fat intake
90.9  (12.8) 95.4  (9.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronic Pancreatitis (CP) Subjects
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments a priori threshold for statistical significance <0.05
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Bomb Calorimetry: Difference in Mean Stool Energy Loss Between Groups: Subjects With CP Compared to Healthy Subjects
Hide Description 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.
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Chronic Pancreatitis (CP) Subjects Healthy Controls
Hide Arm/Group Description:
As part of the primary assessment, CP subjects will eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, and collect stool over 72 hours.
Healthy controls will eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, and collect stool over 72 hours.
Overall Number of Participants Analyzed 21 19
Mean (Standard Deviation)
Unit of Measure: calories/gram of stool
5728  (717) 5171  (393)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronic Pancreatitis (CP) Subjects, Healthy Controls
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments a priori threshold for statistical significance <0.05
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Bomb Calorimetry: Difference in Mean Energy Loss Between Groups: Subjects With CP Before and After Creon36™
Hide Description 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.
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Two subjects were excluded from follow-up due to inadequate stool provision. Two subjects were excluded due to failing the internal validation protocol.
Arm/Group Title Chronic Pancreatitis (CP) Subjects
Hide Arm/Group Description:

For Visit 1, CP subjects will eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, and collect stool over 72 hours.

Subjects will take Creon36™ for 9 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 and the day of Visit 2.

Visit 2 will repeat Visit 1 study procedures.

Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: calories/gram of stool
5702  (691)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronic Pancreatitis (CP) Subjects
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments a priori threshold for statistical significance <0.05
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Malabsorption Blood Test: Difference in Mean HA AUC Between Groups: Subjects With CP Before and After Creon36™
Hide Description 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.
Time Frame 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Chronic Pancreatitis (CP) Subjects
Hide Arm/Group Description:

For Visit 1, 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 prior to MBT breakfast consumption and each hour for 8 hours after consumption, and consume a low-fat study lunch at hour 6 during the test.

Subjects will take Creon36™ for 9 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 and the day of Visit 2.

Visit 2 will repeat Visit 1 study procedures.

Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: mg*h/dL
9.4  (4.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronic Pancreatitis (CP) Subjects
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments a priori threshold for statistical significance <0.05
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Coefficient of Fat Absorption: Difference in Mean % Dietary Fat Absorption Between Groups: Subjects With CP Before and After Creon36™
Hide Description 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.
Time Frame 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Chronic Pancreatitis (CP) Subjects
Hide Arm/Group Description:

For Visit 1, CP subjects will eat a moderate fat diet for 4 days during home diet and stool collection, maintain a 3-day food record, and collect stool over 72 hours.

Subjects will take Creon36™ for 9 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 and the day of Visit 2.

Visit 2 will repeat Visit 1 study procedures.

Overall Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: % of dietary fat intake
93  (8.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronic Pancreatitis (CP) Subjects
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments a priori threshold for statistical significance <0.05
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 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 Event Reporting Description Adverse events were collected by personal interview during the visit itself, and by phone call after the completion of study procedures.
 
Arm/Group Title Chronic Pancreatitis (CP) Subjects Healthy Controls
Hide Arm/Group Description 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™. 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.
All-Cause Mortality
Chronic Pancreatitis (CP) Subjects Healthy Controls
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)      0/24 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Chronic Pancreatitis (CP) Subjects Healthy Controls
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Chronic Pancreatitis (CP) Subjects Healthy Controls
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/24 (29.17%)      3/24 (12.50%)    
Gastrointestinal disorders     
Abdominal Pain/Discomfort   7/24 (29.17%)  7 3/24 (12.50%)  3
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Virginia Stallings, MD
Organization: Children's Hospital of Philadelphia
Phone: 267.425.1633
EMail: stallingsv@email.chop.edu
Layout table for additonal information
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT02849704     History of Changes
Other Study ID Numbers: 16-013001
First Submitted: July 27, 2016
First Posted: July 29, 2016
Results First Submitted: February 26, 2019
Results First Posted: May 3, 2019
Last Update Posted: May 3, 2019