Pancrelipase With Nutritional Supplement in Patients at Risk of Malnutrition (EFFORT-ENZO)

Effect of Low Dose Pancrelipase With an Oral Nutritional Supplement to Improve Nutrient Bioavailability in Patients at Increased Risk of Malnutrition

This study investigates if pancreatic enzymes in combination with oral nutritional supplement can improve nutrient bioavailability in older people with malnutrition or at risk of malnutrition.

Study Overview

• Status: Recruiting
• Conditions: Malnutrition
• Intervention / Treatment: Drug: Zenpep; Drug: Placebo

Detailed Description

This study investigates whether adding digestive pancreatic enzymes to oral nutritional supplements (ONS) can improve nutrient absorption in older adults at risk of malnutrition. While ONS are commonly recommended, their effectiveness is often limited due to age-related declines in exocrine pancreatic function, leading to reduced enzyme secretion. Studies indicate that pancreatic lipase levels decline with age, potentially impairing nutrient digestion and absorption.

The study proposes using pancrelipase (Zenpep®), an FDA-approved pancreatic enzyme replacement therapy, to enhance nutrient bioavailability. The randomized, placebo-controlled trial will assess whether pancrelipase improves postprandial levels of amino acids, fatty acids, and glucose in hospitalized patients at nutritional risk.

The study aims to determine if pancreatic enzyme supplementation can enhance nutrient absorption and provide a novel strategy for managing malnutrition in older adults without diagnosed exocrine pancreatic insufficiency (EPI). If successful, this approach could improve clinical outcomes, reduce healthcare costs, and enhance quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philipp Schuetz, Prof. MD; Phone Number: +41 62 838 68 80; Email: philipp.schuetz@ksa.ch
• Study Contact Backup: Name: Carla Wunderle; Email: carla.wunderle@ksa.ch

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Recruiting
    • Kantonsspital Aarau
    • Contact: Philipp Schuetz, Prof. MD; Phone Number: +41 62 838 68 80; Email: philipp.schuetz@ksa.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Male or female 70 years of age or older
• Hospitalized at site
• Nutrition Risk Screening 2002 (NRS-2002) ≥ 3
• eGFR ≥ 30 mL/min/1.73 m2 (EPI-CKD) based on medical history (no older than 6 months)
• Ability to eat orally

Exclusion Criteria:

• Patients with acute cardiovascular event ≤ 2 days
• Patients with terminal conditions
• Patients diagnosed with pancreatic exocrine insufficiency (EPI) treated with pancreatic enzyme replacement therapy (PERT)
• Patients having a planned transplant or new-onset dialysis in the next 6 months.
• Patients having a colectomy, resection of the small intestine or cholecystectomy
• Known hypersensitivity to any of the substances or excipients of the ONS or the medicinal product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pancrelipase; two capsules each containing 15000 USP units of lipase	Drug: Zenpep; two capsules (each containing 15000 USP units of lipase) together with nutritional supplements; Other Names: Pancrelipase
Placebo Comparator: Placebo; two capsules each containing placebo	Drug: Placebo; two capsules (containing placebo) together with nutritional supplements; Other Names: lactose monohydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental area under the curve of total branched-chained amino acid concentration	Evaluation of the incremental area under the curve (iAUC) of total branched-chain amino acid (BCAA) concentration in blood, including leucine (μmol/L), isoleucine (μmol/L), and valine (μmol/L). The iAUC represents the time-dependent changes in BCAA levels and is used to assess metabolic responses.	From oral nutritional supplements (ONS) consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental area under the curve of essential amino acids (EAAs)	Evaluation of the incremental area under the curve (iAUC) of essential amino acids (EAAs) in plasma, expressed in micromoles per liter (μmol/L). The iAUC reflects the time-dependent changes in EAAs concentrations and is used to assess metabolic responses.	From ONS consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)
Incremental area under the curve of total amino acids	Evaluation of the incremental area under the curve (iAUC) of total amino acids in plasma, expressed in micromoles per liter (μmol/L). The iAUC reflects the time-dependent changes in total amino acid concentrations and is used to assess metabolic responses.	From ONS consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)
Incremental area under the curve of free fatty acids	Evaluation of the incremental area under the curve (iAUC) of free fatty acids in plasma, expressed in micromoles per liter (μmol/L). The iAUC reflects the time-dependent changes in free fatty acid concentrations and is used to assess metabolic responses.	From ONS consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)
Incremental area under the curve of triglycerides	Evaluation of the incremental area under the curve (iAUC) of triglycerides in plasma, expressed in millimoles per liter (mmol/L). The iAUC reflects the time-dependent changes in triglycerides concentrations and is used to assess metabolic responses.	From ONS consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)
Water load satiety test (WLST)	Values of a modified water load satiety test (WLST), a questionnaire of 5 sub-scores on a scale of 1-100. We will report both the sum of the scores and the 5 individual sub scales will be reported. Participant rate pre-and postprandial intensity of symptoms for fullness, hunger, abdominal discomfort, bloating, and nausea on a 0-100 mm visual analogue scale where 0 is none, and 100 is severe	From ONS consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)
Exploratory subgroup analysis	Exploratory subgroup analyses to test their effect on the primary outcome (incremental area under the curve (AUC) of total branched-chained amino acid concentration in the blood) will be performed. These will be assessed using a t-test on the differences between pancrelipase and placebo for each patient. Groups are based on the subgroup including median age [years], malnutrition risk [Nutritional Risk Screening 2002 total score], median weight [kg], sex [male/female], prior history of gastrointestinal side effects [yes/no], median fecal elastase [μg/g]	After study completion, within 1 year
Incremental area under the curve of glucose	Evaluation of the incremental area under the curve (iAUC) of glucose in plasma, expressed in millimoles per liter (mmol/L). The iAUC reflects the time-dependent changes in glucose concentrations and is used to assess metabolic responses.	From ONS consumption over 3 hours postprandial, specifically in 5 time points (T0 ONS consumption and after 30, 60, 120 and 180 minutes)

Collaborators and Investigators

• Sponsor: Philipp Schuetz
• Investigators: Principal Investigator: Philipp Schuetz, Prof. MD, Kantonsspital Aarau

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Oral nutritional supplements; Pancrelipase
• Additional Relevant MeSH Terms: Nutrition Disorders; Nutritional and Metabolic Diseases; Malnutrition; Hydrolases; Enzymes; Enzymes and Coenzymes; Complex Mixtures; Lipase; Carboxylic Ester Hydrolases; Esterases; Pancreatic Extracts; Tissue Extracts; Pancrelipase
• Other Study ID Numbers: 2024-02519; ka24Schuetz

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No