Chronic Pancreatitis, Exocrine Pancreatic Insufficiency, Recurrent Acute Pancreatitis
Conditions
Keywords
Malabsorption Blood Test(MBT), Chronic pancreatitis, Recurrent Acute pancreatitis, Exocrine Pancreatic Insufficiency
Brief summary
This project uses the Malabsorption Blood Test (MBT) to identify patients with recurrent acute or chronic pancreatitis who have mild to moderate exocrine pancreatic insufficiency. A subgroup of patients who have response to pancreatic enzyme replacement therapy will enter a randomized, placebo-controlled pilot clinical trial for 8 weeks to identify improvements in quality of life (QOL).
Detailed description
This proposal uses a blood test detection method for EPI specifically designed to detect fat malabsorption in the setting of inadequate release of pancreatic digestive enzymes. The purpose of using it in this study is to identify mild and moderate EPI, for which to date no reliable test exists. The MBT evaluates the absorption of heptadecanoic acid (HA), a fatty acid dependent on lipase to release it from more complex form before it can be absorbed. Steatorrhea (fatty diarrhea) is a symptom present in over half of subjects with severe EPI, but is frequently not present in mild or moderate forms of EPI. In the absence of overt steatorrhea, there exists no reliable test to detect mild or moderate EPI in subjects with RAP or CP or track response to treatment. Without detection, RAP and CP subjects are at risk for malnutrition if they cannot properly absorb dietary fat and nutrients, and simultaneously significant weight loss, sarcopenia, osteopathy, nutritional deficiencies, GI symptoms and QOL. There is a clear medical need to identify subjects with pancreatic fat malabsorption who will benefit from treatment for EPI - pancreatic enzyme replacement therapy (PERT). In the proposed work, the investigators will enroll 80 subjects with RAP or CP who do not have steatorrhea or known severe EPI, and perform the MBT before and after 5 days of PERT therapy to identify subjects with fat malabsorption responsive to PERT. The investigators will assess clinical factors that correlate with PERT-responsive fat malabsorption. The primary outcome for assessment of the MBT results will be prevalence of PERT-responsive fat malabsorption. It is anticipated that 33% of subjects will have PERT-responsive fat malabsorption. The investigators will then sequentially enroll 24 PERT-responders to an 8-week pilot randomized placebo-controlled clinical trial of PERT supplementation (144,000 lipase units per day) versus placebo to determine the effects on QOL. The hypothesis is that PERT will result in improvement of QOL defined by a positive change from baseline in the PROMIS 29+2 in PERT-responders. PROMIS Gastrointestinal Scales will be assessed as secondary outcomes. Change in the results of a short physical performance battery and changes in body morphology (weight, BMI) from beginning of the study will be assessed in an exploratory fashion for correlation with PERT administration versus placebo.
Interventions
12 participants who are PERT responders in the MBT will be randomized to receive 8 weeks of PERT (144,000 lipase units daily)
DRUGPlacebo
12 participants who are PERT responders in the MBT will be assigned to receive 8 weeks of placebo therapy
DIAGNOSTIC_TESTMBT1
MBT off PERT
DIAGNOSTIC_TESTMBT 2
MBT on PERT
Sponsors
Anna Evans Phillips
Johns Hopkins University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Children's Hospital of Philadelphia
Digestive Care, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
All enrolled subjects will undergo 2 Malabsorption Blood Tests(MBT), one off PERT \[MBT1\], and one on PERT \[MBT2\]) to determine their fat malabsorption response to PERT. Those who have an increase in Heptadecanoic Acid absorption on PERT will be determined to be responders to PERT. Of those subjects that are deemed to be responders, the first 24 will be randomized to the second phase of the study, which is a randomized placebo-controlled clinical trial (RCT). Subjects in the RCT will be given 8 weeks of PERT or 8 weeks of placebo and Quality of Life Measures will be determined at the outset and completion of the trial to assess changes that associate with PERT use compared to placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age * RAP (≥ 2 documented lifetime attacks with ≥ 2 of 3 acute pancreatitis criteria) OR Chronic pancreatitis (Cambridge I or II with documented history of AP OR Cambridge III or IV criteria) * Fecal elastase ≥ 50 within the preceding 12 months
Exclusion criteria
* Allergy/Intolerance to PERT/MBT * Taking medications that alter fat absorption or that supplement the fatty acids being studied (e.g. orlistat, ursodeoxycholic acid, Fatty-15 fatty acid supplement etc.) * Taking GLP-1 Receptor Agonist therapy * Fecal elastase \<50 within preceding 12 months OR pre-existing diagnosis of severe Exocrine Pancreatic Insufficiency, or ongoing steatorrhea * Receiving Pancreatic Enzyme Replacement Therapy for \> 5 days within the preceding 30 days * Acute Pancreatitis attack (documented and meeting at least 2 of 3 criteria) within the preceding 90 days * History of pancreatic resection or underlying malabsorptive disease * Pregnant or Breast Feeding * Other significant medical condition as judged by Principal Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome (Aim 1) | 2 weeks | The primary outcome of the first phase of the study will be the prevalence of responders to PERT by assessing Heptadecanoic Acid absorption following 5-days of PERT therapy compared to baseline (no PERT therapy). This will be measured by a positive area under the curve of the difference between absorption curves for Triheptadecanoic Acid and Pentadecanoic Acid. |
| Primary Outcome (Aim 2) | Baseline (at time of entry to RCT) to completion of RCT, 8 weeks | The primary outcome of the second phase of the study will be change in the Overall Quality of Life Score of the Patient Reported Outcomes Measurement Systems (PROMIS) 29 + 2 questionnaire for subjects receiving PERT compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome: PROMIS Gastrointestinal Symptom Score for Belly Pain | 8 weeks | The PROMIS gastrointestinal symptoms short form for belly pain will be used to track symptoms of EPI over the course of the 8 week trial and change in this will be assessed comparing the cohorts receiving PERT and placebo. Range 0-25. Higher score equals worse belly pain. |
| Secondary Outcome: PROMIS Gastrointestinal Scale for Bowel Incontinence | 8 weeks | The PROMIS gastrointestinal symptoms short form for bowel incontinence will be used to track symptoms of EPI over the course of the 8 week trial. This will be assessed as a secondary outcomes, comparing change between the cohorts receiving PERT and placebo. Range 4-20. Higher score equals more bowel incontinence. |
| Secondary Outcome: PROMIS Gastrointestinal Scale for Constipation | 8 weeks | The PROMIS gastrointestinal symptoms short form for constipation will be used to track symptoms of EPI over the course of the 8 week trial. This will be assessed as a secondary outcome, comparing change between the cohorts receiving PERT and placebo. Ragne 8-45. Higher score equals worse constipation. |
| Secondary Outcome: PROMIS Gastrointestinal Scale for Diarrhea | 8 weeks | The PROMIS gastrointestinal symptoms short form for diarrhea will be used to track symptoms of EPI over the course of the 8 week trial. This will be assessed as a secondary outcome, comparing change between the cohorts receiving PERT and placebo. Range 5-30. Higher score equals worse diarrhea. |
| Secondary Outcome: PROMIS Gastrointestinal Scale for Nausea and Vomiting | 8 weeks | The PROMIS gastrointestinal symptoms short form for nausea and vomiting will be used to track symptoms of EPI over the course of the 8 week trial. This will be assessed as a secondary outcome, comparing change between the cohorts receiving PERT and placebo. Range 3-20. Higher score equals worse nausea and vomiting. |
| Secondary Outcome: PROMIS Gastrointestinal Scale for Gas and Bloating | 8 weeks | The PROMIS gastrointestinal symptoms short form for gas and bloating will be used to track symptoms of EPI over the course of the 8 week trial. This will be assessed as a secondary outcome, comparing change between the cohorts receiving PERT and placebo. Ragne 4-65. Higher score equals worse gas and bloating. |
Countries
United States
Contacts
CONTACTAnna E Phillips, MD MS
PRINCIPAL_INVESTIGATORAnna E Phillips, MD MS
University of Pittsburgh
Outcome results
None listed