A Phase 3 interventional study of Dietary Supplement: Pancreatic enzyme preparation from microbial source that contains amylase (6650 DU), lipase (13000 FIP), and protease (7120 HUT, 15 SAPU, 3000 PC). and Standard of care porcine pancreatic enzyme preparation: amylase (8000 U), lipase (25000 U), and protease (1000 U) in Pancreatitis, Chronic and Exocrine Pancreatic Insufficiency (EPI), sponsored by Asian Institute of Gastroenterology, India. Not yet recruiting. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by Asian Institute of Gastroenterology, India · Phase 3, Interventional, and Treatment
Background: Chronic pancreatitis (CP) is a progressive inflammatory disorder causing irreversible pancreatic damage, eventually resulting in pancreatic exocrine insufficiency (PEI). This may lead to malabsorption, malnutrition, weight loss, and impaired quality of life. Pancreatic enzyme replacement therapy (PERT) is the standard treatment for PEI and is predominantly derived from porcine sources. However, religious, ethical, dietary, and supply-related concerns highlight the need for effective non-porcine alternatives. Microbial (fungal)-based pancreatic enzymes have shown promising safety and efficacy in preliminary studies, but evidence in CP remains limited.
Objective: To compare the efficacy and safety of non-porcine microbial (fungal)-based pancreatin with standard porcine-based pancreatin in patients with PEI secondary to CP.
Methods: This investigator-initiated, randomized, double-blind, single-center, non-inferiority trial will enroll 134 adults with CP-associated PEI (defined as having a fecal elastase \<100 µg/g). After a two-week washout period, participants will be randomized 1:1 to receive either microbial-based or porcine-based pancreatin for 12 weeks. The primary outcome is the change from baseline in the Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) score at 12 weeks. Secondary outcomes include nutritional status, anthropometric measures, gastrointestinal symptoms, pain scores, stool consistency, glycaemic parameters, laboratory markers, and quality of life.
Discussion: This study aims to evaluate whether microbial-based pancreatin is non-inferior to porcine-based therapy and may provide a culturally acceptable and sustainable alternative for managing CP-related PEI.
Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas. It is characterized by persistent inflammation that progressively damages the pancreatic tissue, leading to irreversible fibrotic changes. The dominant clinical manifestation of is abdominal pain and ongoing parenchymal injury leads to a gradual decline in both exocrine and endocrine function. However, the onset of pancreatic exocrine insufficiency (PEI) and diabetes is not universal, as a subset of individuals with CP retains sufficient exocrine reserve to avoid clinically significant malabsorption. When functional decline advances, however, patients may ultimately develop PEI and diabetes. In the absence of disease-modifying treatments, the current primary goal of management is early recognition and management of these complications. Treatment includes pain management, digestive support with pancreatic enzyme supplementation and nutrition, and endocrine management with oral antidiabetic medications and/or insulin.
In PEI, insufficient secretion of pancreatic enzymes leads to inadequate digestion and absorption of nutrients, resulting in weight loss, malnutrition, metabolic bone disease, and deficiencies of fat-soluble vitamins and minerals. PEI develops frequently in patients with CP, with a prevalence ranging from 30%-85% within 10-15 years after diagnosis.
Large cohort studies report an overall PEI prevalence of 50%-75%, particularly in patients with alcohol-related CP and longer disease duration. Management of PEI secondary to CP is important to improve nutritional status and quality of life. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for PEI. According to two meta-analyses, supportive treatment with pancreatic enzyme replacement showed significant improvement in the symptoms and consequences of PEI in patients with CP.
Currently available PERT preparations are primarily derived from porcine pancreas. Although clinically effective, porcine-derived PERT has certain limitations, including concerns related to its animal origin. Additionally, some patients may avoid such supplements due to lifestyle or ethical choices, such as vegetarians and vegans, while others, particularly followers of Islam and Judaism, may refrain from porcine-derived products due to religious dietary restrictions. Importantly, there is an increased lack of supplies due to the increasing prevalence of CP and other diseases associated with PEI. Therefore, new formulations of PERT are an unmet need.
Advances in biotechnology have led to the development of non-porcine microbial (fungal) based pancreatic enzymes that have been shown to have a good safety profile and efficacy in several conditions. Animal studies and human pilot studies have also shown benefit in CP. While the use of porcine PERT is well-established in CP, the utilization of non-porcine microbial-based PERT and its efficacy in CP is unclear.
HYPOTHESIS:
We hypothesize that non-porcine PERT will be as efficacious as the porcine based pancreatic enzymes in nutrient digestion. Hence, the aim of this study is to evaluate the clinical efficacy of non-porcine, microbial-based pancreatic enzymes compared with the current standard of care porcine enzymes, as a supportive therapy for patients with PEI secondary to CP.
REPORTING:
The study protocol will reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 guidelines.
MONITORING:
The conduct of the study will be monitored by a Data Safety Monitoring Board (DSMB).
STUDY DESIGN AND DURATION:
This is a multi-center, randomized, double-blind, parallel-group (1:1), placebo-controlled, non-inferior trial. The trial duration is 3 months (including enrolment and follow-up period). The study will be conducted in three independent branches of AIG hospitals, at Gachibowli, Somajiguda, and Banjara Hills, Hyderabad, India. The main branch at Gachibowli will be the coordinating center. Ethical approval has already been procured in the coordinating center (Asian Institute of Gastroenterology, Gachibowli).
FOLLOW-UP PLAN The patients will be provided with a structured diary wherein they will record their body weight every week using the same weighing machine for all measurements to ensure consistency. They will also record their medication intake, new symptoms, need for hospital visits, and any deviation in their diet regimen. A research coordinator will make a telephone call to each patient after weeks 4, 6, and 8 to collect any data that the patient recorded over the weeks. At the same time, the coordinator will also ensure and encourage compliance with the treatment. At the end of the study, the patient will visit the study centers where all the baseline measurements will be repeated. The patients will be directed to bring the study medicine containers, and a pill count will be done.
RANDOMIZATION, BLINDING, AND PERT ALLOCATION:
After obtaining written informed consent by the designated research coordinator, eligible participants who satisfy the inclusion criteria and complete the 2-week wash-out period will be randomized in a 1:1 ratio to either the non-porcine microbial (bacterial + fungal)-based pancreatin group or the porcine-based standard-of-care pancreatin group. A block randomization method with a block size of 8 will be used to ensure equal allocation between the two groups. Randomization will be performed using a sealed envelope randomization software (https://www.sealedenvelope.com/power/continuous-noninferior/) by a statistician who is not involved in patient interaction, study interventions, or data analysis. Treatment allocation and blinding will be managed by an independent research coordinator not involved in the conduct of the study or patient care.
The principal investigator (PI), co-investigators, study staff, outcome assessors, and participants will remain blinded to treatment allocation throughout the study to ensure unbiased treatment administration and outcome assessment.
Unblinding will be permitted only in the event of a medical emergency or serious adverse event where knowledge of the assigned intervention is essential for clinical management. The PI will authorize unblinding and access the allocation code for the specific participant through the secure randomization system. The reason and date of unblinding will be documented, and the Institutional Ethics Committee will be notified as per regulatory requirements. Unblinding will be restricted to the affected participant and will not compromise the overall blinding of the trial.
STUDY AND ASSESSMENT METHOD:
Once the initial screening is completed by the PI and participant allocation is performed by an independent research coordinator, the designated co-investigators and research team from each center will systematically assess and record clinical, radiological (baseline), biochemical, and treatment-related details.
SAMPLE SIZE CALCULATION:
The study is designed as a non-inferiority trial comparing non-porcine microbial (fungal)based with porcine-based standard of care pancreatin on the primary continuous outcome measured by the PEI-Q total score (range 0-72). Non inferiority will be concluded if the upper bound of the one-sided 97.5% confidence interval for the mean difference does not exceed a pre-specified non-inferiority margin of 10 units, which is considered the minimal clinically important difference for the PEI-Q based on expert consensus. Sample size and power calculations for a range of non-inferiority margins (Δ = 5, 7.5, 10, 12.5, and 15 units), assuming a common standard deviation of 15 units and n = 60 participants per group, indicate that the study has approximately 94% power to demonstrate non-inferiority for a margin of 10 units, with higher power for larger margins and lower power for smaller margins. To adjust for 10% drop-outs, we will increase to sample size to 67 patients in each group adding up to a total of 134 patients.
STATISTICAL ANALYSIS A centralized database will be developed in RedCAP. Data will be uploaded from the three study centers and curated at the monitoring center in Aalborg, Denmark. All analyses will be conducted at the University of Aalborg, who will be blinded to treatment allocation and randomization.
Continuous variables will be expressed as mean with standard deviation (SD) or median with interquartile range (IQR), as appropriate. Categorical variables will be presented as frequencies and proportions.
A linear mixed-effects model will be used to assess changes in PEI-Q scores across all assessment time points. Summary statistics with corresponding 95% confidence intervals (CI) will be reported with the between group-difference at 12 weeks being the primary endpoint.
Continues secondary outcomes, including changes in nutritional parameters, SARC-F score, stool consistency, gastrointestinal symptom severity, quality of life, endocrine function, fecal elastase-1 levels, and body composition, will be analyzed using mixed-effects regression models for normally distributed variables and quantile regression models for non-normally distributed variables. Categorical outcomes will be analyzed using risk differences between groups with corresponding 95% confidence intervals.
Missing data will be handled using multiple imputation techniques. A two-tailed p-value of \<0.05 will be considered statistically significant.
Exclusion Criteria:
The non-porcine microbial enzyme preparation will contain amylase (6650 DU), lipase (13000 FIP), and protease (7120 HUT, 15 SAPU, 3000 PC)
Dietary Supplement: Dietary Supplement: Pancreatic enzyme preparation from microbial source that contains amylase (6650 DU), lipase (13000 FIP), and protease (7120 HUT, 15 SAPU, 3000 PC).
The standard of care porcine-based enzyme preparation will contain amylase (8000 U), lipase (25000 U), and protease (1000 U)
Other: Standard of care porcine pancreatic enzyme preparation: amylase (8000 U), lipase (25000 U), and protease (1000 U)
Dietary Supplement: Pancreatic enzyme preparation from microbial source that contains amylase (6650 DU), lipase (13000 FIP), and protease (7120 HUT, 15 SAPU, 3000 PC).
Standard of care porcine pancreatic enzyme preparation: amylase (8000 U), lipase (25000 U), and protease (1000 U)
Change in Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) score
The PEI-Q is a validated questionnaire that captures several symptoms related to exocrine pancreatic insufficiency and the result is presented as a composite score.
Time frame: 3 months
Change in nutritional status: Subjective global assessment
Subjective global assessment (SGA) is a composite semi-quantitative tool that provides the degree of nutrition of an individual in three categories such as SGA A (Normal nutrition), SGA B (moderate malnutrition) and SGA C (Severe malnutrition).
Time frame: 3 months
Change in nutritional status: Body weight
Percent change in body weight (kg)
Time frame: 3 months
Change in nutritional status: Anthropometry
Mid-arm circumference (MAC) in cm.
Time frame: 3 months
Change in nutritional status: Anthropometry
Mid-upper arm muscle circumference (MAMC) in cm.
Time frame: 3 months
Change in nutritional status: Anthropomentry
Mid-arm muscle area (MAMA) in cm square.
Time frame: 3 months
Change in nutritional status: Anthropomentry
Triceps skin fold thickness (TSF) in cms.
Time frame: 3 months
Change in nutritional status: Biochemical assessment
Hemoglobin in gm/dL
Time frame: 3 months
Change in nutritional status: Biochemical assessment
Serum pre albumin (mg/dl)
Time frame: 3 months
Change in nutritional status: Biochemical assessment
Vitamin D
Time frame: 3 months
Change in nutritional status: Biochemical assessment
Vitamin B12
Time frame: 3 months
Change in quality of life
Quality of life will be assessed by the Short Form (SF)-36 tool. This is a standardised and validated questionnaire based scoring tool that contains 36 questions dealing with 8 domains of quality of life. The lowest score in this tool is 0 and the highest score is 100, a higher score indicating better quality of life.
Time frame: 3 months
Change in endocrine status
HbA1c
Time frame: 3 months
Change in endocrine function
Fasting blood glucose (mg/dl)
Time frame: 3 months
Change in endocrine function
C-peptide
Time frame: 3 months
Change in body composition (Bioimpedence analysis): Body fat mass (kg)
Total body fat will be assessed using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body. The normal range is 10-20kg.
Time frame: 3 months
Change in body composition (Bioimpedence analysis): Skeletal muscle mass (kg)
Skeletal muscle mass will be assessed using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body
Time frame: 3 months
Change in body composition (Bioimpedence analysis): Total body water (litres)
Total body water will be quantified using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body.
Time frame: 3 months
Change in body composition (Bioimpedence analysis): Phase angle at 50kH (degrees)
Cell membrane integrity will be assessed using the phase angle function of Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body.
Time frame: 3 months
Change in body composition (Bioimpedence analysis): Visceral fat level (numerical unit; normal range (1-12).
Visceral fat level will be assessed using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body. The normal range is from 1-12, a loser value indicating lower visceral fat and higher value indicates larger visceral fat.
Time frame: 3 months
Stool consistency
Bristol stool scale \[Type 1 (separate hard lumps, indicating constipation) to Type 7 (watery stool, indicating diarrhea\].
Time frame: 3 months
Change in gastrointestinal symptoms
Patient Assessment of Upper Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM)
Time frame: 3 months
Change in sarcopenia score
SARC-F Questionnaire (Score of =/\>4 is considered to have sarcopenia)
Time frame: 3 months
Change in patient's global impression of change (PGIC)
This will be evaluated using the Patient's Global Impression of Change (PGIC). The score ranges from 1-7, with a score of 1 indicating very much improved and 7 indicating very much worse
Time frame: 3 months
Change in quality of life (QOL)
QOL will be assessed using the EORTC-QLQ c30 with PAN-28.
Time frame: 3 months
Change in pain severity
Range of 0-10 in the Visual Analog Scale (VAS). A score of 0 indicates no pain, while 10 is maximum pain.
Time frame: 3 months.
Change in pain severity
Pain-related symptoms and characteristics will be assessed using the Short-form Comprehensive Pain Assessment Tool (COMPAT-SF).
Time frame: 3 months
Readmission during the study period
Number of admissions during the study period
Time frame: 3 months
Change in functional mobility during the study period.
This will be performed using the using the Timed Up and Go (TUG) test.
Time frame: 3 months.
No study locations are listed for this record.
Plan to share: Undecided
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Asian Institute of Gastroenterology, India