Targeted Nutritional Intervention (HMB, Arginine, Glutamine) in Patients With Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with cancer cachexia, a condition characterized by progressive loss of skeletal muscle mass and strength driven by systemic inflammation. Recent evidence suggests that chemotherapy and tumor-related inflammation disrupt the gut-muscle axis, leading to increased intestinal permeability and bacterial imbalance (dysbiosis), which further worsen muscle loss. The purpose of this pilot study is to evaluate whether an early, targeted nutritional supplement containing beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-glutamine can preserve or increase skeletal muscle mass in patients with locally advanced pancreatic ductal adenocarcinoma starting systemic chemotherapy. Participants will be randomly assigned to one of two groups: * Experimental group: receives standard dietary counseling plus an oral nutritional supplement (Abound, containing beta-hydroxy-beta-methylbutyrate, L-arginine, and L-glutamine) twice daily for 60 days, starting 7 to 10 days before the first cycle of chemotherapy. * Control group: receives standard dietary counseling alone. The total study participation for each patient is 60 days, during which changes in muscle mass, muscle quality, physical function, quality of life, and blood and stool biomarkers will be evaluated.

Inclusion Criteria: * Age ≥ 18 years * Histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma (PDAC) * Locally advanced disease stage (non-metastatic) * Eligibility and scheduled to start first-line systemic chemotherapy (either in neoadjuvant or adjuvant setting) * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 * Estimated life expectancy \> 3 months * Ability to maintain adequate regular oral food intake * Signed written informed consent to participate in the study and for biological sample storage Exclusion Criteria: * Presence of distant metastatic disease * Severe renal impairment (creatinine clearance \< 30 mL/min) or decompensated liver disease (Child-Pugh class C, unrelated to PDAC) * Active intestinal obstruction, sub-occlusion, or severe gastrointestinal disorder preventing oral feeding * Exclusive Total Parenteral Nutrition (TPN) * Known hypersensitivity or allergy to any component of the study nutritional supplement (Abound: HMB, L-Arginine, L-Glutamine) * Regular use of dietary supplements containing beta-hydroxy-beta-methylbutyrate (HMB), L-glutamine, or L-arginine within 30 days prior to study enrollment