Blood Flow Restriction Exercise in Patients With Pancreatic, Biliary Tract, and Liver Cancer (PREV-Ex)

Study Overview
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Brief Summary
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In patients with cancer, resistance training appears to be a safe and effective exercise modality to increase both lean muscle mass and strength, as well as attenuates cancer-related fatigue. It may serve as a feasible intervention in these patients to mitigate cachexia, especially if implemented before the onset of cancer cachexia or in a pre-cachectic state. This study is a multicenter randomized controlled trial that will compare a blood flow restricted resistance training intervention during the pre- (prehabilitation) and post-operative (rehabilitation) phase in patients with pancreatic, biliary tract and liver cancer, versus usual care on skeletal muscle and other health-related outcomes.

Official Title
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Blood Flow Restriction Exercise in the Perioperative Setting to Prevent the Loss of Muscle Mass in Patients With Pancreatic, Biliary Tract, and Liver Cancer - the PREV-Ex Randomized Controlled Trial

Conditions
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Pancreatic Cancer, Biliary Tract Cancer, Liver Cancer

Intervention / Treatment
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* Other: Physical exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of resectable pancreatic cancer Diagnosis of resectable biliary tract cancer (includes cholangiocarcinoma and ampullary cancer) Diagnosis of resectable liver cancer ECOG (Eastern Cooperative Oncology Group scale) performance status ≤ 2 Exclusion Criteria: Serious active infection Uncontrolled severe pain Severe neurologic or cardiac impairment according ACSM criteria Uncontrolled severe respiratory insufficiency as determined by the treating clinician Any other contraindications for exercise as determined by the treating physician Poor Swedish comprehension Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise group<br>The experimental group will in addition to standard care receive supervised and home-based exercise training program with a specific focus to induce metabolic stress (blood flow restriction exercise), and protein supplementation to ensure adequate protein intake. | Other: Physical exercise<br>* The intervention group will receive an exercise program consisting of a combination of supervised and home-based exercise with a focus to induce metabolic stress (blood flow restriction exercise) during both a pre- and postoperative period consisting of a total of 5-6 weeks. Protein supplementation will be given to exclude insufficient intake.<br>|
| No Intervention: Usual care<br>The control group will in addition to standard care receive protein supplementation to ensure adequate protein intake. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle thickness | Skeletal muscle thickness (mm) measured through ultrasound | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Skeletal muscle cross sectional area | Skeletal muscle cross sectional area (um2) measured through ultrasound | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle morphology | Skeletal muscle morphology (au) measured through microscopy methods in skeletal muscle biopsies | Change from baseline to: 2 weeks, 8 weeks | 
| Skeletal muscle protein levels | Skeletal muscle protein levels (au) measured through western blot in skeletal muscle biopsies | Change from baseline to: 2 weeks, 8 weeks | 
| Skeletal muscle metabolism | Skeletal muscle metabolism (au) measured through biochemical methods in skeletal muscle biopsies | Change from baseline to: 2 weeks, 8 weeks | 
| Body lean mass | Lean mass (kg) measured through bioimpedance and CT scan | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Body fat mass | Fat mass (kg) measured through bioimpedance and CT scan | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Handgrip strength | Maximal handgrip strength (kg) measured through hand dynamometry | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Lower limb muscle strength | Maximal led strength (kg) measured through isometric force measurements | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Health-related quality of life | Disease specific helath related quality of life measured with The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) Summary Score (0-100 points with a higher score indicating a better quality of life) | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Physical performance | Short Physical Performance Battery (SPPB score points ranging from 0-12 with a higher score indicating a better physical function) measured through handgrip strength test, leg strength test, endurance test | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Cancer-related fatigue | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Fatigue12 (EORTC-QLQ-FA12) Summary Score (0-100 points with a higher score indicating a better quality of life) | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Nutritional status | Subjective Global Assessment Form scores (score ranging between 7 (normal) and 35 (severely malnourished) | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Participants' experience of the exercise program | Focus group interviews | 8 weeks | 
| Treatment related complications | days to recover after surgery | 4 weeks | 
| Treatment related complications | days to recover after surgery | 8 weeks | 
| Treatment related complications | days to recover after surgery | 16 weeks | 
| Hospitalization | days of being hospitalized | 4 weeks | 
| Hospitalization | days of being hospitalized | 8 weeks | 
| Hospitalization | days of being hospitalized | 16 weeks | 
| Physical activity | Measured through an activity tracker (hours) | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Diastolic blood pressure | Diastolic blood pressure (mmHg) measured at rest | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Systolic blood pressure | Systolic blood pressure (mmHg) measured at rest | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks | 
| Endothelial function | Measured through the passive leg movement (PLM) technique through ultrasound measurements (blood flow in mL/min) | Change from baseline to: 2 weeks, 4 weeks, 8 weeks, 16 weeks |