A Nutrition and Exercise Program With Olanzapine Compared to Olanzapine Alone: A Trial in Patients With Advanced Tumors (SwissNutriAct2)

A Nutrition and Exercise Program With Olanzapine Compared to Olanzapine Alone: A Randomized Controlled Intervention Trial in Patients With Advanced Tumors

Cancer patients have a higher risk of malnutrition because of their illness and treatments. This can lead to weight loss, weak muscles, less effective cancer therapy, or stronger side effects.

This research project looks at whether adding a combined nutrition and exercise program to the standard treatment for appetite loss (olanzapine) can improve the quality of life for patients with cancer, compared to taking olanzapine alone.

In this study, patients are randomly split into two groups. The program group gets advice from nutrition experts and physiotherapists. They also receive a nutritional supplement containing whey protein, leucine, and HMB (substances that help protect muscles). The control group continues their usual cancer treatment without the extra nutrition and exercise program. Both groups receive olanzapine as part of their standard care to treat loss of appetite, and both keep a diary to track their progress.

Information will be collected at the start of the study, as well as after 6, 12, and 24 weeks.

Nutritional advice and exercise are safe, easy-to-use steps that can help patients with cancer, especially when done together.

Study Overview

• Status: Not yet recruiting
• Conditions: Malnutrition; Cancer, Advanced Solid Tumors
• Intervention / Treatment: Behavioral: Standardized nutritional program; Behavioral: standardized exercize program; Dietary supplement: Whey protein supplement with added leucine and β-hydroxy-β-methylbutyrate (HMB)

Detailed Description

Cancer-related malnutrition represents a major clinical challenge. It is characterized by involuntary weight loss, muscle wasting, functional decline, reduced quality of life (QoL), longer and more frequent hospitalizations, and an increased risk for complications. Together, these factors substantially increase healthcare costs.

Despite growing awareness, evidence from robust randomized trials on multimodal interventions remains limited. Effective management requires a coordinated, multidisciplinary, and multimodal strategy.

The combination of nutritional counseling, physical exercise, and olanzapine (an ASCO-recommended appetite stimulant used according to standard care) may synergistically improve QoL (primary endpoint; Functional Assessment of Cancer Therapy - General; FACT-G), as well as nutritional status, energy intake, fatigue, muscle mass, and strength (secondary endpoints) in patients with advanced cancer.

With this prospective, randomized controlled trial, we aim to investigate whether adding a structured nutrition and exercise intervention to olanzapine improves QoL after 12 weeks of the program, compared to olanzapine alone.

Eligible outpatients with metastatic or locally advanced solid tumors and appetite loss will be randomized to either:

1. an intervention group receiving personalized nutrition counseling and a physical exercise program, in combination with a leucine and β-hydroxy β-methylbutyrate (HMB)-enriched whey protein supplement; or
2. a control group receiving standard oncological care.

All participants will receive low-dose olanzapine for the treatment of appetite loss according to standard clinical care, with treatment initiated after the baseline assessment at the start of the 12-week program.

Both arms will be assessed at baseline (0 weeks), after the 12-week intervention phase, and at a follow-up assessment after 24 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lucia Gafner, Dr. sc. nat.; Phone Number: +41 52 266 21 37; Email: lucia.gafner@ksw.ch
• Study Contact Backup: Name: Esther Gerrits, Dr. med.; Phone Number: +41 52 266 38 10; Email: esther.gerrits@ksw.ch

Study Locations

• Switzerland
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Metastatic or locally advanced solid tumors, excluding lymphoma, not eligible for curative treatment
• VAS score ≤70 for appetite, as defined for anorexia in oncology patients (olanzapine is prescribed according to clinical guidelines as part of standard care)
• WHO-PS of ≤3
• Ability to participate in physical exercise, as judged by the treating oncologist
• Anticipated life expectancy of at least six months
• Willingness to provide written informed consent

Exclusion Criteria:

• Pregnancy or breastfeeding
• Parkinson's disease, known risk for narrow-angle glaucoma, or any other contraindication to olanzapine, as judged by the treating oncologist
• Alcohol consumption >2 units/d
• Use of Olanzapine for any indication for more than four days per month
• Current use of any antipsychotic or antidepressant medication
• Recent use of systemic corticosteroids (prednisolone ≥10 mg/d or equivalent) for more than seven days within the past four weeks
• Presence of ascites at time of enrolment
• Concurrent radiotherapy to the esophagus
• Intake of products with added high-dose BCAA (branched-chain amino acids, total ≥3 g/d) within the past month
• Tube feeding and/or parenteral nutrition within the previous month (excluding ONS (oral nutritional supplements)
• History of ileus within the past month
• Allergy to milk protein
• Inability to comprehend trial information due to language barriers, cognitive or psychological limitations, or disease-related factors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard care.
Experimental: Intervention; Nutrition and exercise program including a nutritional supplement.	Behavioral: Standardized nutritional program; The nutritional intervention includes a comprehensive 45-60 minute initial assessment with the study dietitian and personalized dietary recommendations and individualized interventions. Counseling comprises at least three sessions. During follow-up visits, nutritional status is reassessed and interventions are adapted as needed.; Behavioral: standardized exercize program; The structured exercise program includes at least three visits with the study physiotherapist, starting with a comprehensive 45-60 minute initial assessment. The training regimen is re-evaluated at least twice. The program emphasizes home-based strength and endurance training, aiming to meet or exceed the guidelines of the WHO and the American Cancer Society: 2.5 hours of moderate- or 1.25 hours of high-intensity activity per week, or an equivalent combination thereof.; Dietary supplement: Whey protein supplement with added leucine and β-hydroxy-β-methylbutyrate (HMB); The whey protein supplement high in leucine and β-hydroxy-β-methylbutyrate (HMB) is ingested once daily, preferably in the evening or post-exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QoL)	Questionnaire Functional Assessment of Cancer Therapy - General (FACT-G). Total scores range from 0-108 points, with higher scores reflecting better QoL.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional status	Bioelectrical impedance analysis (BIA)	3 months
Nutritional status	Muscle mass: L3 image of computertomographic (CT) measurements taken in the context of standard cancer therapy (divided by height squared; in cm2/m2)	3 months
Clinical data	Physical performance status (WHO performance status, grade 0-5)	3 months
Nutritional status	Body weight (in kg), used in combination with body height to calculate BMI (kg/m2)	3 months.
Nutritional status	Calf circumference (cm)	3 months
Physical function	Handgrip strength	3 months
Physical function	60-second sit-to-stand test	3 months
Physical function	6-minute walk test	3 months
Energy- and protein intake	Data collected with food diaries; Harris-Benedic formula	3 months
Adherence to the nutrition and exercise program	Completed counseling sessions; supplement intake; adherence based on data recorded in the journal	3 months
Succes of recruitment rate in comparison to former studies	Number of eligible patients, participants, rejections as compared to similar past studies	Throughout recruitment phase.
Clinical data	Overall survival	3 months
Clinical data	Adverse events (AEs) grade 3 and 4	3 months
Clinical data	Serious adverse events (SAEs; unplanned hospitalizations)	3 months
Clinical data	Progression free survival	3 months
Fatigue	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Total scores range from 0-52 points, with higher scores reflecting less pronounced fatigue.	3 months
Nutritional status	Sarcopenia questionnaire: sarcopenia functional assessment (SARC-F). Total scores range from 0-10 points, with higher scores reflecting higher sarcopenia risk.	3 months
Nutritional status	Patient-generated subjective global assessment, short form, PG-SGA SF. Lower scores reflect better nutritional status.	3 months
Nutritional status	Global Leadership Initiative of Malnutrition (GLIM) criteria, a diagnositic tool for malnutrition, focusing on phenotypic and etiologic criteria.	3 months
Appetite	Visucal analog scale (VAS) for appetite. Total scores range from 0-100, with higher scores reflecting better Appetite.	3 months
Appetite	Anorexia-cachexia scale (A/CS). Total scores range from 0-48 points, with higher scores reflecting better Appetite.	3 months

Collaborators and Investigators

• Sponsor: Kantonsspital Winterthur KSW
• Collaborators: Krebsforschung Schweiz, Bern, Switzerland; Sponser Sport Food AG; HOCH Health Ostschweiz, Kantonsspital St. Gallen
• Investigators: Principal Investigator: Christian Britschgi, PD Dr. med. Dr. phil., Kantonsspital Winterthur KSW

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 20, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Cancer; Quality of Life; Nutrition; Protein supplementation; Olanzapine; HMB; Leucine; Palliative
• Additional Relevant MeSH Terms: Nutrition Disorders; Behavior; Nutritional and Metabolic Diseases; Malnutrition; Neoplasms; Motor Activity
• Other Study ID Numbers: 2026-00199

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data (IPD) with other researchers.

Drug and device information, study documents

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