Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Gastro-esophageal Cancer Clinical Trial

Official title:

Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05650827
• Other study ID #: 18.10.22
• Status: Recruiting
• Phase: N/A
• Start date: February 24, 2023
• Est. completion date: December 2027

Study information

• Verified date: April 2023
• Source: Rigshospitalet, Denmark
• Contact: Rikke Krabek, MD
• Phone: +4535457641
• Email: rikke.krabek[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with advanced gastroesophageal cancer are in great risk of losing skeletal muscle mass and developing cancer cachexia. Low skeletal muscle mass has a negative impact on quality of life, impairs physical function, increases toxicity from anti-neoplastic treatment, as well as increases risk of death.

Resistance training and protein supplements have the potential to stimulate muscle anabolism and counteract loss of skeletal muscle mass. Therefore, the investigators have designed a randomized controlled feasibility trial to evaluate the feasibility, safety and the therapeutic effect of resistance training and protein supplements in patients with advanced gastroesophageal cancer undergoing first line chemotherapy.

A total of 54 patients with advanced gastroesophageal cancer will be recruited from the Department of Oncology, Copenhagen University Hospital, Rigshospitalet and randomly allocated 2:1 to standard care plus resistance training 3 times pr. week and a daily supplement of protein or to standard care alone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• histologically verified, non-resectable cancer of the esophagus, stomach, or gastroesophageal junction

• referred to first line chemotherapy.

Exclusion Criteria:

• Age < 18

• Living outside the greater Copenhagen area

• Any other malignancy requiring active treatment

• Not eligible for chemotherapy

• Performance status > 2

• Not able to swallow liquids

• Parenteral nutrition or enteral nutrition via feeding tube

• Physical or mental disabilities that prohibit execution of test or training procedures

• Pregnancy

• Inability to understand the Danish language

Related Conditions & MeSH terms

• Gastro-esophageal Cancer

Intervention

Behavioral:
• Resistance training
10 weeks of resistance training 3 times pr. week.

Dietary Supplement:
• Protein supplement
A daily supplement of protein to ensure a daily intake of 1,6g protein/kg bodyweight

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood biochemistry: Leukocyte differential counts	Changes in differential counts (total and per type: eosinofils, basofils, neutrofils, monocytes and lymphocytes)	Baseline, end of week 10
Other	Blood biochemistry: C-reactive protein	Changes in C-reactive protein	Baseline, end of week 10
Other	Blood biochemistry: albumin and protein	Changes in albumine and protein	Baseline, end of week 10
Other	Blood biochemistry: magnesium and phosphate	Changes in magnesium and phosphate	Baseline, end of week 10
Other	Blood biochemistry: Total cholesterol	Changes in total cholesterol	Baseline, end of week 10
Other	Blood biochemistry: Low-density lipoprotein cholesterol	Changes in low-density lipoprotein cholesterol	Baseline, end of week 10
Other	Blood biochemistry: High-density lipoprotein cholesterol	Changes in high-density lipoprotein cholesterol	Baseline, end of week 10
Other	Blood biochemistry: Triglyceride	Changes in triglyceride	Baseline, end of week 10
Other	Blood biochemistry: Glycated hemoglobin A1c	Changes in glycated hemoglobin A1c	Baseline, end of week 10
Other	Blood biochemistry: Insulin	Changes in insulin	Baseline, end of week 10
Other	Blood biochemistry: Glucose tolerance	Changes in glucose tolerance (2-hpur oral glucose tolerance test)	Baseline, end of week 10
Other	Blood biochemistry: Glucose	Changes in glucose	Baseline, end of week 10
Other	Blood biochemistry: C-peptide	Changes in c-peptide	Baseline, end of week 10
Other	Blood biochemistry: Interleukin-1	Changes in interlieukin-1	Baseline, end of week 10
Other	Blood biochemistry: Interleukin-6	Changes in interlieukin-6	Baseline, end of week 10
Other	Blood biochemistry: Interleukin-8	Changes in interlieukin-8	Baseline, end of week 10
Other	Blood biochemistry: Interleukin-10	Changes in interlieukin-10	Baseline, end of week 10
Other	Blood biochemistry: Interferon-gamma	Changes in interferon-gamma	Baseline, end of week 10
Other	Blood biochemistry: Tumor necrosis factor-alpha	Changes in tumor necrosis factor-alpha	Baseline, end of week 10
Other	Blood biochemistry: Circulating tumor DNA	Changes in circulating tumor DNA	Baseline, week 5 and 10
Other	Effect of acute exercise: Insulin sensitivity	Muscle glucose uptake during insulin stimulation after acute exercise	Immediately after acute exercise
Other	Effect of acute exercise: muscle protein synthesis	Muscle protein synthesis during insulin stimulation after acute exercise.	Immediately after acute exercise
Other	Changes of proteins in muscle biopsies	Modifications of proteins after acute exercise. Muscle biopsies will be subjected to mass spectrometry-based proteomic analysis.	Before and immediately after acute exercise
Other	Changes of proteins in mithocondrial regulation	Modifications of mithochondrial regulation. Signaling of mitochondiral fission, fusion and mitophagy will be examined in mucle biopsies.	Before and immediately after acute exercise
Primary	Exercise feasibility: Exercise sessions attendance	The number of attended exercise training sessions relative to the number of planed exercise sessions	From baseline until end of intervention (10 weeks)
Primary	Exercise feasibility: Relative dose-intensity of protein supplement	The actual amount consumed relative to the amount prescribed over the intervention period	From baseline until end of intervention (10 weeks)
Primary	Incidence of Serious Adverse Events (SAEs).	SAE will be recorded during trial assessment visits and through medical records. This procedure will concern any SAE during the trial period. For each trial visit we will collect patients' self-report of SAEs, which may have occurred during the period since the last trial visit.	Baseline until end of intervention (10 weeks)
Secondary	Exercise feasibility: Relative dose intensity of exercise	The actual dose relative to the prescribed minimum dose	Baseline until end of intervention (10 weeks)
Secondary	Exercise feasibility: Early termination of exercise sessions	Termination of an exercise session before the prescribed exercises have been performed	Baseline until end of intervention (10 weeks)
Secondary	Exercise feasibility: Exercise intervention interruptions	Incidence of exercise intervention disruptions, defined as a period of = 7 days without an attended exercise session	Baseline until end of intervention (10 weeks)
Secondary	Exercise feasibility: Permanent discontinuation	Incidence of permanent withdrawal from the intervention before intervention period has ended.	Baseline until end of intervention (10 weeks)
Secondary	Body composition and anthropometrics: Total lean mass	Changes in total lean mass, assessed by dual energy x-ray absorptiometry (DXA)	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Appendicular lean mass	Changes in appendicular lean mass, assessed by DXA	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Total fat mass	Changes in total fat mass, assessed by DXA	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Fat percentage	Changes in fat percentage, assessed by DXA	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Bone mineral density	Changes in bone mineral density, assessed by DXA	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Muscle thickness	Changes in thickness of the vastus lateralis, assessed by ultrasound	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Skeletal muscle index	Changes in skeletal muscle index, assessed by diagnostic CT scans	At diagnose, after 10 weeks intervention and at 1 year follow up
Secondary	Body composition and anthropometrics: Skeletal muscle attenuation	Changes in skeletal muscle attenuation, assessed by diagnostic CT scans	At diagnose, end of week 10
Secondary	Body composition and anthropometrics: Adipose tissue index	Changes in adipose tissue index, assessed by diagnostic CT scans	At diagnose, end of week 10
Secondary	Body composition and anthropometrics: Body mass	Changes in body mass	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Body mass index	Changes in body mass index	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Hip circumference	Changes in hip circumference	Baseline, end of week 10
Secondary	Body composition and anthropometrics: Waist circumference	Changes in waist circumference	Baseline, end of week 10
Secondary	Muscle strength: Leg press maximal muscle strenght	Changes in leg press one repetition maximum (1RM)	Baseline, end of week 10
Secondary	Muscle strength: Chest press maximal muscle strenght	Changes in chest press 1RM	Baseline, end of week 10
Secondary	Muscle strength: Hand grip strenght	Changes in hand grip strength, assessed using a dynamometer	Baseline, end of week 10
Secondary	Functional performance: Habituel gait speed	Changes in habitual gait speed	Baseline, end of week 10
Secondary	Functional performance: Maximal gait speed	Changes in maximal gait speed	Baseline, end of week 10
Secondary	Functional performance: Sit-to-stand	Changes in sit-to-stand power.	Baseline, end of week 10
Secondary	Functional performance: Stair climb	Changes in stair climbing power	Baseline, end of week 10
Secondary	Resting metabolic rate	Changes in resting metabolic rate	Baseline, end of week 10
Secondary	Blood pressure: Systolic blood pressure	Changes in systolic blood pressure	Baseline, end of week 10
Secondary	Blood pressure: Diastolic blood pressure	Changes in diastolic blood pressure	Baseline, end of week 10
Secondary	Heart rate	Changes in resting heart rate	Baseline, end of week 10
Secondary	1 and 2-years cancer-specific survival	Proportion of patients who have not died from gastroesophageal cancer 1 and 2 years after randomization	Randomization to 1 and 2 years after randomization
Secondary	1 and 2-years over-all survival	Proportion of patients who have not died 1 and 2 years after randomization	Randomization to 1 and 2 years after randomization
Secondary	Progression-free survival	Time to progression	Randomization to 2 years after randomization
Secondary	Treatment tolerance: Hospitalization	Unscheduled hospitalization	3, 6 and 9 weeks after randomization
Secondary	Treatment tolerance: Relative dose intensity	Treatment tolerance assessed by the delivery of chemotherapy (relative dose intensity)	3, 6 and 9 weeks after randomization
Secondary	Treatment tolerance: Number of series recieved	Treatment tolerance assessed by the delivery of chemotherapy (number of series recieved)	3, 6 and 9 weeks after randomization
Secondary	Treatment tolerance: Tolerated dose	Treatment tolerance assessed by the delivery of chemotherapy (dose reduction)	3, 6 and 9 weeks after randomization
Secondary	Treatment tolerance: Permanent discontinuation of the treatment	Treatment tolerance assessed by the delivery of chemotherapy (permanent discontinuation of the treatment)	3, 6 and 9 weeks after randomization
Secondary	Treatment effect: Response to chemotherapy	Response to chemotherapy assessed by Response Evaluation Criteria in Solid Tumors 1.1 (complete response, partiel response, stable disease, progressive disease)	Randomization to 2 years after randomization
Secondary	Health-related quality of life: Physical well-being	Changes in patient-reported physical well-being assessed using the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) (scale-scoring 0-28, the higher the score the better quality of life)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Health-related quality of life: Social well-being	Changes in patient-reported social well-being assessed using FACT-E (scale-scoring 0-28, the higher the score the better quality of life)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Health-related quality of life: Emotional well-being	Changes in patient-reported social well-being assessed using FACT-E (scale-scoring 0-24, the higher the score the better quality of life)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Health-related quality of life: Functional well-being	Changes in patient-reported functional well-being assessed using FACT-E (scale-scoring 0-28, the higher the score the better quality of life)	Baseline,10 weeks-, 1 year-, 2 years after randomization
Secondary	Health-related quality of life: gastroesophageal cancer specific	Changes in patient-reported gastroesophageal cancer specific well-being assessed using FACT-E (scale-scoring 0-68, the higher the score the better quality of life)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Health-related quality of life: cancer cachexia specific	Changes in patient-reported cancer cachexia specific well-being assessed using Functional Assessment of Cancer Therapy - Cancer Cachexia (scale-scoring 0-48, the higher the score the better quality of life)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Depression	Changes in patient-reported depression, assessed using the Hospital Anxiety and Depression Scale (HADS) (scale scoring: 0-21, the higher the score the worse the condition)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Anxiety	Changes in patient-reported anxiety, assessed using the HADS (scale scoring: 0-21, the higher the score the worse the condition)	Baseline, 10 weeks-, 1 year-, and 2 years after randomization
Secondary	Self-reported physical activity: Walking	Changes in patient-reported weekly duration of walking, assessed using the International Physical Activity Questionnaire (IPAQ)	Baseline, end of week 10
Secondary	Self-reported physical activity: Moderate intensity physical activity (PA)	Changes in patient-reported weekly duration of moderate intensity PA, assessed using the IPAQ	Baseline, end of week 10
Secondary	Self-reported physical activity: Vigorous intensity PA	Changes in patient-reported weekly duration of vigorous intensity PA, assessed using the IPAQ	Baseline, end of week 10
Secondary	Self-reported physical activity: Total PA	Changes in patient-reported weekly duration of total PA, assessed using the IPAQ (Expressed as metabolic equivalent (MET)-min per week: MET level x minutes of activity x events per week)	Baseline, end of week 10
Secondary	Self-reported physical activity: Sitting time	Changes in patient-reported weekly duration of sitting time, assessed using the IPAQ	Baseline, end of week 10
Secondary	Self-reported screening of sarcopenia	Changes in patient-reported signs of sarcopenia, assessed using The Strength, assistance in walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire (scale scoring: 0-10, the higher the score the better the condition)	Baseline, end of week 10
Secondary	Self-reported three-days dietary records	Changes in patient-reported three-day record of dietary intake assessed using questionnaries.	Baseline, week 5 and week 10
Secondary	Patient-reported symptomatic adverse events	Patient-reported symptomatic adverse events, assessed using the using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	One week after each serie of chemotherapy during the intervention (10 weeks)