Effects of Peptamen 1.6 in Malnourished Patients (or at Risk) With Pancreatic Neoplasia Undergoing Cephalic Pancreaticoduodenectomy (CPD): A Mechanistic Study

Effects of Peptamen 1.6 in Malnourished Patients (or in Risk) With Pancreatic Neoplasia Undergoing Cephalic Pancreaticoduodenectomy (CPD): A Study Mechanistic.

Malnutrition is a common challenge in patients with pancreatic cancer undergoing cephalic pancreaticoduodenectomy (CPD), impacting postoperative recovery and overall prognosis. Nutritional support plays a crucial role in optimising metabolic, inflammatory, and digestive outcomes. This randomised, double-blind, crossover clinical trial aims to evaluate the effects of Peptamen 1.6, a hydrolysed whey protein-based enteral formula, compared to Resource HP/HC, a high-protein and high-calorie polymeric formula, in malnourished or at-risk patients with pancreatic cancer undergoing PD.

The study comprises both in vivo and in vitro analyses. The in vivo component will assess the impact of Peptamen 1.6 on digestive tolerance, amino acid absorption, nutritional status, metabolic profile, inflammatory markers, and gut microbiota composition. The in vitro component will utilise human intestinal organoid models to explore how enteral nutrition formulations influence intestinal permeability and metabolism, with a focus on microbiota interactions.

Primary outcomes include improvements in metabolic status, assessed through serum biomarkers (albumin, immune markers, intestinal permeability, and myosin profile), inflammatory status via peripheral blood mononuclear cells (PBMCs), and microbiota shifts in faecal samples. Additionally, adherence to treatment, digestive tolerance, and changes in body composition will be monitored using bioelectrical impedance, dynamometry, and functional mobility tests.

By elucidating the mechanisms through which different enteral nutrition strategies influence clinical, physiological, and molecular parameters, this study aims to enhance personalised nutritional interventions for patients with pancreatic cancer. The findings could contribute to optimising nutritional support strategies, ultimately improving patient outcomes following CPD.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer, Adult; Cephalic Duodenopancreatectomy
• Intervention / Treatment: Dietary supplement: Dietary Supplement: Experimental Treatment with nutritional suplement A + nutritional suplement B; Dietary supplement: Dietary Supplement: Dietary Supplement: Experimental Treatment with nutritional suplement B + nutritional suplement A

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

Contacts and Locations

• Study Contact: Name: Gabriel Olveira Fuster, MD, PhD; Phone Number: 951290343; Email: gabrielm.olveira.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Málaga
    • Málaga, Málaga, Spain, 29009
      • Recruiting
      • Hospital Regional Universitario de Málaga
      • Contact: Gabriel Olveira Fuster, MD, PhD; Phone Number: 951290343; Email: gabrielm.olveira.sspa@juntadeandalucia.es

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ambulatory patients who are malnourished or at risk of malnutrition, with a confirmed diagnosis of neoplasms of the periampullary region, pancreas, and duodenum, or pancreatic cancer, and who have undergone cephalic pancreaticoduodenectomy (CPD).
• No prior neoadjuvant treatment (preoperative chemotherapy or radiotherapy): Patients must not have received neoadjuvant therapy as these treatments can affect metabolism, nutritional status, and gut microbiota, potentially interfering with the objectives of the study's nutritional intervention.

Exclusion Criteria:

• Refusal to sign informed consent: Informed consent is a mandatory requirement for study participation. Any patient unwilling to participate voluntarily will be excluded.
• Patients who underwent surgery more than three months ago will be excluded, as the nutritional intervention must begin in the immediate postoperative period to adequately evaluate its impact on nutritional and metabolic status.
• Presence of severe cardiac disease, nephropathy, or other severe comorbidities: Conditions such as severe cardiac disease, renal failure, or comorbidities that could induce malnutrition or impair the patient's ability to tolerate nutritional treatment will be exclusion criteria. These conditions may interfere with assessing the effects of nutritional supplementation in the context of pancreatic cancer treatment.
• Diarrhoea associated with antibiotics, laxatives, or osmotically active agents: Diarrhoea caused by medications may alter nutrient absorption and affect tolerance to the nutritional supplement, potentially skewing results attributable solely to the nutritional intervention.
• Treatment with other nutritional support: Patients receiving other oral nutritional supplement, enteral or parenteral nutrition will be excluded, as interactions with the studied formula could confound the efficacy results of the study's nutritional intervention.
• Pregnancy or possibility of becoming pregnant.
• Type 1 or Type 2 diabetes with HbA1c >8%.
• Galactosaemia, fructosaemia, or allergies to components of the nutritional supplement.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXPERIMENTAL GROUP A (Nutritional supplement order A --> B)	Dietary supplement: Dietary Supplement: Experimental Treatment with nutritional suplement A + nutritional suplement B; Intervention group will receive a nutritional formula A and, after 1-week washout period, will receive a nutritional formula B
Experimental: EXPERIMENTAL : EXPERIMENTAL GROUP B (Nutritional supplement order B --> A)	Dietary supplement: Dietary Supplement: Dietary Supplement: Experimental Treatment with nutritional suplement B + nutritional suplement A; Intervention group will receive a nutritional formula B and, after 1-week washout period, will receive a nutritional formula A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to nutritional treatment	Categorized based on the average daily consumption compared to the prescribed volume (200 ml per bottle): Full content (200 ml/bottle); 2/3 content (150 ml/bottle); 1/2 content (100 ml/bottle); 1/4 content (50 ml/bottle) Patients will self-report their average daily consumption (ml/day).	At weeks 6 and 13
Natural food intake	Patients will report their food intake over the previous week, categorized into quartiles (%) relative to: Pre-illness consumption; Perceived normal intake for patients without supplementationALL -100%3/4 - 75%HALF - 50%¼ - 25%NONE - 0%	At weeks 6 and 13
Tolerance to nutritional treatment	Evaluated based on the frequency of gastrointestinal symptoms (e.g., nausea, vomiting, reflux, abdominal pain, flatulence, satiety, constipation, and stomach heaviness) within two hours of supplement consumption. Symptoms classified as: Never; Rarely; Sometimes; Frequently; Always Bivariate analysis will classify tolerance as: Good (no symptoms); Poor (presence of any gastrointestinal symptoms)	At weeks 6 and 13
Change in aminoacids: Ala, Glu, Asp, Pro, Phe, Leu/Ile, Val, Tyr, Met, Cit, Arg, Gly, and Orn	Aminoacids measured in µmol/L	At baseline and in weeks 6, 7, and 13
Change in IL-6 and TNF-alpha RNA expression	IL-6 and TNF-alpha measured from Peripheral blood mononuclear cell (PBMC)	At baseline and in weeks 6, 7, and 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Doses of pancreatic enzyme replacement therapy	Measured in International Unit per day (IU/day)	Only at baseline
Stool characteristics	The number and type of stools will be assessed using the Kings Stool Chart, a standardized tool that classifies stool consistency and form to evaluate digestive function alterations.; Number of bowel movements: A numerical field to record the daily count.; Type of bowel movements: A categorical field with options ranging from 1 to 7, based on the King's Stool Chart.; Variability in type: A binary field (0 = No, 1 = Yes) to indicate whether there is variation.	At baseline and in weeks 6, 7, and 13
Symptoms of anxiety and depression	Measured using the Hospital Anxiety and Depression Scale (HADS), which consists of two subscales: HADS-Anxiety (HADSA) and HADS-Depression (HADSD) Interpretation of scores: 0-7: Normal.; 8-10: Suggests the presence of mood disorders.; ≥11: Indicates a probable mood disorder.	At baseline and in weeks 6, 7, and 13
Nutritional status	Evaluated using the Subjective Global Assessment (SGA) and Global Leadership Initiative on Malnutrition (GLIM) criteria, both validated tools for classifying malnutrition severity. Patients will be categorized as at risk of malnutrition or having moderate or severe malnutrition based on results.	At baseline and in weeks 6, 7, and 13
Change in Phase angle (PhA) (Vectorial Bioimpedance Analysis (BIVA))	Phase angle (PhA) measured in degrees (º)	At baseline and in weeks 6, 7, and 13
Change in total body water (TBW) (Vectorial Bioimpedance Analysis (BIVA))	Total body water (TBW) measured in liters (l)	At baseline and in weeks 6, 7, and 13
Change in extracellular water (ECW) (Vectorial Bioimpedance Analysis (BIVA))	Extracellular water (ECW) measured in liters (l)	At baseline and in weeks 6, 7, and 13
Change in intracellular water (ICW) (Vectorial Bioimpedance Analysis (BIVA))	Intracellular water (ICW) measured in liters (l)	At baseline and in weeks 6, 7, and 13
Change in Fat-free mass (FFM) (Vectorial Bioimpedance Analysis (BIVA))	Fat-free mass (FFM) measured in kilograms (kg) and percentage (%)	At baseline and in weeks 6, 7, and 13
Change in Fat mass (FM) (Vectorial Bioimpedance Analysis (BIVA))	Fat mass (FM) measured in kilograms (kg) and percentage (%)	At baseline and in weeks 6, 7, and 13
Change in Body cell mass (BCM) (Vectorial Bioimpedance Analysis (BIVA))	Body cell mass (BCM) measured in kilograms (kg)	At baseline and in weeks 6, 7, and 13
Change in appendicular skeletal muscle mass (ASMM) (Vectorial Bioimpedance Analysis (BIVA))	Appendicular skeletal muscle mass (ASMM) measured in kilograms (kg)	At baseline and in weeks 6, 7, and 13
Change in skeletal muscle index (SMI) (Vectorial Bioimpedance Analysis (BIVA))	Skeletal muscle index (SMI) measured in kilogram per square meter (kg/m²)	At baseline and in weeks 6, 7, and 13
Change in hydration (Vectorial Bioimpedance Analysis (BIVA))	Hydration measured in percentage (%)	At baseline and in weeks 6, 7, and 13
Change in resistance (Vectorial Bioimpedance Analysis (BIVA))	Resistance measured in ohms (Ω)	At baseline and in weeks 6, 7, and 13
Change in reactance (Vectorial Bioimpedance Analysis (BIVA))	Reactance measured in ohms (Ω)	At baseline and in weeks 6, 7, and 13
Handgrip dynamometry	Device: Jamar hydraulic dynamometer; Measurement: Mean and maximum grip strength (kg) from three measurements Used to assess sarcopenia	At baseline and in weeks 6, 7, and 13
Timed Up and Go (TUG) Test	Measures mobility and physical function; Procedure: Time (seconds) taken for the patient to:Rise from a chairWalk a short distanceReturn to the chair	At baseline and in weeks 6, 7, and 13
Change in total fat (Abdominal Ultrasound)	Total fat measured in centimeters (cm)	At baseline and in weeks 6, 7, and 13
Change in superficial fat (Abdominal Ultrasound)	Superficial fat measured in centimeters (cm)	At baseline and in weeks 6, 7, and 13
Change in preperitoneal fat (Abdominal Ultrasound)	Preperitoneal fat measured in centimeters (cm)	At baseline and in weeks 6, 7, and 13
Change in muscle Ultrasound - Area	Area measured in square centimeters (cm²)	At baseline and in weeks 6, 7, and 13
Change in muscle Ultrasound - Circumference	Circumference measured in centimeters (cm)	At baseline and in weeks 6, 7, and 13
Change in muscle Ultrasound - X-axis and Y-axis	X-axis and Y-axis measured in centimeters (cm)	At baseline and in weeks 6, 7, and 13
Change in muscle Ultrasound - Adipose tissue of the rectus femoris of the quadriceps	Adipose tissue of the rectus femoris of the quadriceps measured in centimeters (cm)	At baseline and in weeks 6, 7, and 13
Change in Glucose	glucose measured in mg/dl	At baseline and in weeks 6, 7, and 13
Change in Cholesterol	Cholesterol measured in mg/dl	At baseline and in weeks 6, 7, and 13
Change in Triglycerides	Triglycerides measured in mg/dl	At baseline and in weeks 6, 7, and 13
Change in Uric acid	Uric acid measured in mg/dl	At baseline and in weeks 6, 7, and 13
Change in AST	AST measured in units per litre (U/L)	At baseline and in weeks 6, 7, and 13
Change in ALT	ALT measured in units per litre (U/L)	At baseline and in weeks 6, 7, and 13
Change in GGT	GGT measured in units per litre (U/L)	At baseline and in weeks 6, 7, and 13
Change in ALP	ALP measured in units per litre (U/L)	At baseline and in weeks 6, 7, and 13
Change in insulin	Insulin measured in units per mililitre (U/mL)	At baseline and in weeks 6, 7, and 13
Change in albumin	Albumin measured in grams per liter (g/l)	At baseline and in weeks 6, 7, and 13
Change in C-reactive protein (CRP)	C-reactive protein (CRP) measured in milligrams per liter (mg/L)	At baseline and in weeks 6, 7, and 13
Change in Intestinal fatty acid-binding protein (I-FABP)	Intestinal fatty acid-binding protein (I-FABP) measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in zonulin	Zonulin measured in micrograms per milliliter (μg/mL)	At baseline and in weeks 6, 7, and 13
Change in musclin	Musclin measured in nanograms per milliliter (ng/mL)	At baseline and in weeks 6, 7, and 13
Change in galectin-3	Galectin-3 measured in nanograms per milliliter (ng/mL)	At baseline and in weeks 6, 7, and 13
Change in myostatin	Myostatin measured in nanograms per milliliter (ng/mL)	At baseline and in weeks 6, 7, and 13
Change in Total antioxidant capacity (TAC)	Total antioxidant capacity (TAC) measured in nanomoles per microliter (nmol/μL)	At baseline and in weeks 6, 7, and 13
Change in Glutathione peroxidase (GSH-Px)	Glutathione peroxidase (GSH-Px) measured in milliunits per milliliter (mU/mL)	At baseline and in weeks 6, 7, and 13
Change in Superoxide dismutase (SOD)	Superoxide dismutase (SOD) measured in inhibition rate %	At baseline and in weeks 6, 7, and 13
Change in GLP-1	GLP-1 measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in GIP	GIP measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in PYY	PYY measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IFN-gamma	IFN-gamma measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IL-2	IL-2 measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IL-4	IL-4 measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IL-6	IL-6 measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IL-10	IL-10 measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IL-12p70	IL-12p70 measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in IL-17A	IL-17A measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in TNF-alpha	TNF-alpha measured in picograms per milliliter (pg/mL)	At baseline and in weeks 6, 7, and 13
Change in stool calprotectin	Calprotectin measured in micrograms per gram (µg/g)	At baseline and in weeks 6, 7, and 13

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Investigators: Principal Investigator: Gabriel Olveira Fuster, MD, PhD, Hospital Regional Universitario de Málaga, FIMABIS

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 21, 2025
• First Posted (Actual): February 28, 2025

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: pancreaticoduodenectomy; malnutrition; gut microbiota; Pancreatic cancer; oral nutritional supplement; organoids
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Nutritional and Metabolic Diseases; Malnutrition; Pancreatic Neoplasms; Pancreatic cancer, adult
• Other Study ID Numbers: PEP-NUTRIDPC trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is not necessary to reach the objectives of the project

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No