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

N/ARecruitingNCT06852014

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud20 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Interventions

Dietary Supplement: Experimental Treatment with nutritional suplement A + nutritional suplement BDIETARY_SUPPLEMENT

Intervention group will receive a nutritional formula A and, after 1-week washout period, will receive a nutritional formula B

Dietary Supplement: Dietary Supplement: Experimental Treatment with nutritional suplement B + nutritional suplement ADIETARY_SUPPLEMENT

Intervention group will receive a nutritional formula B and, after 1-week washout period, will receive a nutritional formula A

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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).

Time frame: 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 supplementation * ALL -100% * 3/4 - 75% * HALF - 50% * ¼ - 25% * NONE - 0%

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: At baseline and in weeks 6, 7, and 13

Secondary Outcomes

Doses of pancreatic enzyme replacement therapy

Measured in International Unit per day (IU/day)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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 (%)

Time frame: 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 (%)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: At baseline and in weeks 6, 7, and 13

Change in hydration (Vectorial Bioimpedance Analysis (BIVA))

Hydration measured in percentage (%)

Time frame: At baseline and in weeks 6, 7, and 13

Change in resistance (Vectorial Bioimpedance Analysis (BIVA))

Resistance measured in ohms (Ω)

Time frame: At baseline and in weeks 6, 7, and 13

Change in reactance (Vectorial Bioimpedance Analysis (BIVA))

Reactance measured in ohms (Ω)

Time frame: 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

Time frame: 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: 1. Rise from a chair 2. Walk a short distance 3. Return to the chair

Time frame: At baseline and in weeks 6, 7, and 13

Change in total fat (Abdominal Ultrasound)

Total fat measured in centimeters (cm)

Time frame: At baseline and in weeks 6, 7, and 13

Change in superficial fat (Abdominal Ultrasound)

Superficial fat measured in centimeters (cm)

Time frame: At baseline and in weeks 6, 7, and 13

Change in preperitoneal fat (Abdominal Ultrasound)

Preperitoneal fat measured in centimeters (cm)

Time frame: At baseline and in weeks 6, 7, and 13

Change in muscle Ultrasound - Area

Area measured in square centimeters (cm²)

Time frame: At baseline and in weeks 6, 7, and 13

Change in muscle Ultrasound - Circumference

Circumference measured in centimeters (cm)

Time frame: 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)

Time frame: 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)

Time frame: At baseline and in weeks 6, 7, and 13

Change in Glucose

glucose measured in mg/dl

Time frame: At baseline and in weeks 6, 7, and 13

Change in Cholesterol

Cholesterol measured in mg/dl

Time frame: At baseline and in weeks 6, 7, and 13

Change in Triglycerides

Triglycerides measured in mg/dl

Time frame: At baseline and in weeks 6, 7, and 13

Change in Uric acid

Uric acid measured in mg/dl

Time frame: At baseline and in weeks 6, 7, and 13

Change in AST

AST measured in units per litre (U/L)

Time frame: At baseline and in weeks 6, 7, and 13

Change in ALT

ALT measured in units per litre (U/L)

Time frame: At baseline and in weeks 6, 7, and 13

Change in GGT

GGT measured in units per litre (U/L)

Time frame: At baseline and in weeks 6, 7, and 13

Change in ALP

ALP measured in units per litre (U/L)

Time frame: At baseline and in weeks 6, 7, and 13

Change in insulin

Insulin measured in units per mililitre (U/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in albumin

Albumin measured in grams per liter (g/l)

Time frame: 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)

Time frame: 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)

Time frame: At baseline and in weeks 6, 7, and 13

Change in zonulin

Zonulin measured in micrograms per milliliter (μg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in musclin

Musclin measured in nanograms per milliliter (ng/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in galectin-3

Galectin-3 measured in nanograms per milliliter (ng/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in myostatin

Myostatin measured in nanograms per milliliter (ng/mL)

Time frame: 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)

Time frame: 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)

Time frame: At baseline and in weeks 6, 7, and 13

Change in Superoxide dismutase (SOD)

Superoxide dismutase (SOD) measured in inhibition rate %

Time frame: At baseline and in weeks 6, 7, and 13

Change in GLP-1

GLP-1 measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in GIP

GIP measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in PYY

PYY measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IFN-gamma

IFN-gamma measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IL-2

IL-2 measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IL-4

IL-4 measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IL-6

IL-6 measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IL-10

IL-10 measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IL-12p70

IL-12p70 measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in IL-17A

IL-17A measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in TNF-alpha

TNF-alpha measured in picograms per milliliter (pg/mL)

Time frame: At baseline and in weeks 6, 7, and 13

Change in stool calprotectin

Calprotectin measured in micrograms per gram (µg/g)

Time frame: At baseline and in weeks 6, 7, and 13

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts