Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients
- Conditions
- Melanoma
- Interventions
- Other: AEP Group Walking SessionsOther: CEP Group Walking Sessions
- Registration Number
- NCT05615883
- Lead Sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Brief Summary
This study is designed to investigate the effects of ketogenic milieu induced by acute exercise as well as the effects of recurrent exercise bouts on functional status and the accumulation in peripheral blood of MDSCs and the consequent balance on antitumor immunity in melanoma patients.
- Detailed Description
The screening period starts once a patient has provided written informed consent to participate in the study and ends on the day of exercise initiation. Screening assessments have to be done within 28 days prior to exercise initiation. The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations. After the sign of an informed consensus, patients will be assigned to a specific exercise program. The first series of patients will be assigned to the Acute Exercise Program (AEP group), the second series to the Chronic Exercise Program (CEP group). The protocol will be implemented in the time between diagnosis and surgical intervention without any delay in the therapeutic pathway.
Basal evaluation: patient's life style will be investigated using the short version of Physical Activity Questionnaire (Italian version) and MeDiet questionnaire. Age, weight and eight will be registered for all patients. The Lean Body Mass will be measured by Dual Energy X-ray Absorptiometry (DEXA). A cardiorespiratory test will be performed to calculate an appropriate exercise intensity and subsequently the Six Minutes WalkingTest and the Comfortable Walking Speed test will be run before exercise protocol. In the CEP group the DEXA and the walking tests will be repeated after the end of exercise program.
Exercise prescription: the physical exercise consists in walking at a brisk pace. In order to produce a constant metabolic stress in patients with different aerobic power, walking intensity will be prescribed in accordance with the method of the Heart Rate Reserve (HRR), ie difference between resting heart rate (HR-resting) and the heart rate corresponding to muscle's maximal oxygen uptake (HR-max). This prescribing method is based on the linear relationship between heart rate reserve and muscle workload calculated as a percentage of the difference between resting and maximum muscle oxygen consumption (VO2R%). The training intensity will be set to the 30% HRR, the lowest intensity that produces a training effect. To minimize the impact of the research protocol on the patient's therapeutic path, the investigators refrain from the execution of a Cardio Pulmonary Exercise Test and therefore opted for calculating the HR-max using the ACSM formula. Given the entry criteria of this study the investigators believe this choice will minimally affect the exercise-dose prescription and study results.
Acute Exercise Protocol (AEP): The acute program consists in a single walking session on a treadmill lasting 80 minutes. The exercise session will begin with a 10-minute warm-up at the patient's self selected comfortable speed. On the ending of warm up, treadmill speed will be increased until reaching target HRR zone. Then the treadmill speed will be maintained stable throughout the exercise session. Cardiac workload will be monitored by a Sport-watch (Garmin Forerunner 35) and the walking biomechanics by a foot sensor (Garmin Running Dynamic Pod Sensore).
Chronic Exercise Protocol (CEP): The chronic program consists in a walking session on a treadmill lasting 80 minutes (depending on the AEP results), repeated three time a week for three weeks. The walking intensity will be defined during a treadmill test performed before the beginning of the exercise program. Each exercise session will begin with a 10-minute warm-up at the patient's self selected comfortable speed. On the ending of warm up, patients will increase treadmill speed until reaching target HRR zone. Then the treadmill speed will be maintained stable throughout the exercise session. The first training session will be organized in hospital with supervision of research staff. Cardiac workload will be monitored by a Sport-watch(Garmin Forerunner 35) and walking biomechanics by a foot sensor (Garmin Running Dynamic Pod Sensore).
Diet intervention: Modifications occurring during AEP strictly depend on the baseline metabolic conditions. For this reason, patients must remain fasting for 4 hours before the workout and avoid glucose rich foodies for 120 minutes after the end of exercise session in CEP group. During the exercise session patients will have free access to water only. All patients will complete a food diary during the study period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
- Age from 18 to 65 years at the time of recruitment
- Histologically confirmed diagnosis of primary melanoma
- Patients who are candidate to curative surgery for primary melanoma, skin radicalization or sentinel node biopsy.
- American Society of Anaesthesiologists (ASA) status I
- Willingness and ability to comply with the protocol, the scheduled visits, treatment plans, laboratory tests and other procedures.
- Understanding and signature of the informed consent
- Female patients of childbearing potential must agree to sexual abstinence or to use highly effective method of contraception throughout the study (for CEP patients)
- American Society of Anaesthesiologists (ASA) status > I
- Pregnancy or lactation
- Known infection from HIV virus
- Regular physical exercise (more than 1 exercise workout of moderate to intense exercise activity per week)
- Any physical or mental conditions interfering with the ability to perform exercise or to complete the testing procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description AEP Group AEP Group Walking Sessions First series of patients (10 pts) will be assigned to the Acute Exercise Protocol Group (AEP Group). The acute program consists in a single walking session on a treadmill lasting 80 minutes. The exercise session will begin with a 10-minute warm-up at the patient's self selected comfortable speed. On the ending of warm up, treadmill speed will be increased until reaching target HRR zone. Then the treadmill speed will be maintained stable throughout the exercise session. Cardiac workload will be monitored by a Sport-watch (Garmin Forerunner) and the walking biomechanics by a foot sensor (Garmin Running Dynamic Pod Sensore). CEP Group CEP Group Walking Sessions Second series of patients (10 pts) will be assigned to the Chronic Exercise Protocol Group (CEP Group). The chronic program consists in a walking session on a treadmill lasting 80 minutes (depending on the AEP results), repeated three time a week for three weeks. The walking intensity will be defined during a treadmill test performedbefore the beginning of the exercise program. Each exercise session will beginwith a 10-minute warm-up at the patient's self selected comfortable speed. On the ending of warm up, patients will increase treadmill speed until reaching target HRR zone.Then the treadmill speed will be maintained stable throughout the exercise session. The first training session will be organized in hospital with supervision of research staff. Cardiac workload will be monitored by a Sport-watch (Garmin Forerunner) and walking biomechanics by a foot sensor (Garmin Running Dynamic Pod Sensore).
- Primary Outcome Measures
Name Time Method Analysis of the "systemic metabolic milieu"_AEPInf before AEP group: before exercise. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise) CEP group: up to two weeks of exercise program. Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.
Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise) CEP group: up to two weeks of exercise program. CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).
Analysis of the "systemic metabolic milieu"_AEPMet before AEP group: before exercise. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_AEPLip before AEP group: before exercise. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_AEPHor before AEP group: before exercise. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_AEPcounts before AEP group: before exercise. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_AEPMet 40 AEP group: after 40 minutes of exercise session. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_AEPHor 40 AEP group: after 40 minutes of exercise session. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_AEPInf 40 AEP group: after 40 minutes of exercise session. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_AEPcounts 40 AEP group: after 40 minutes of exercise session. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_AEPMet 80 AEP group: after 80 minutes of exercise session. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_AEPLip 24 AEP group: at 24 post-exercise. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_AEPcounts 24 AEP group: at 24 post-exercise. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_AEPLip 40 AEP group: after 40 minutes of exercise session. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_AEPHor 80 AEP group: after 80 minutes of exercise session. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_AEPInf 80 AEP group: after 80 minutes of exercise session. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_AEPLip 80 AEP group: after 80 minutes of exercise session. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_AEPMet 24 AEP group: at 24 post-exercise. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_AEPHor 24 AEP group: at 24 post-exercise. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_AEPInf 24 AEP group: at 24 post-exercise. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_AEPcounts 80 AEP group: after 80 minutes of exercise session. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_AEPMet 72 AEP group: at 72 hours post-exercise. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_AEPHor 72 AEP group: at 72 hours post-exercise. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_AEPInf 72 AEP group: at 72 hours post-exercise. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_CEPHor before CEP group: before exercise program. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_CEP counts before CEP group: before exercise program. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_AEPLip 72 AEP group: at 72 hours post-exercise. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_AEPcounts 72 AEP group: at 72 hours post-exercise. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_CEPMet before CEP group: before exercise program. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_CEPInf before CEP group: before exercise program. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_CEPLip before CEP group: before exercise program. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_CEPMet 1w CEP group: after one week of exercise program. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_CEPHor 1w CEP group: after one week of exercise program. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_CEPInf 1w CEP group: after one week of exercise program. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_CEPLip 1w CEP group: after one week of exercise program. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the "systemic metabolic milieu"_CEPcounts 1w CEP group: after one week of exercise program. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the "systemic metabolic milieu"_CEPcounts 2w CEP group: up to two week of exercise program. Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.
Analysis of the metabolic parameters by capillary sampling_AEPCap before AEP group: before exercise session. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the metabolic parameters by capillary sampling_AEPCap 40 AEP group: after 40 minutes of exercise session. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the metabolic parameters by capillary sampling_AEPCap 80 AEP group: after 80 minutes of exercise session. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the metabolic parameters by capillary sampling_AEPCap 72 AEP group: at 72 hours post-exercise. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the "systemic metabolic milieu"_CEPMet 2w CEP group: up to two week of exercise program. In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters
Analysis of the "systemic metabolic milieu"_CEPHor 2w CEP group: up to two week of exercise program. In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters
Analysis of the "systemic metabolic milieu"_CEPInf 2w CEP group: up to two week of exercise program. In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters
Analysis of the "systemic metabolic milieu"_CEPLip 2w CEP group: up to two week of exercise program. We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes
Analysis of the metabolic parameters by capillary sampling_CEPCap before CEP group: during the first training session Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the metabolic parameters by capillary sampling_AEPCap 24 AEP group: at 24 post-exercise. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the metabolic parameters by capillary sampling_CEPCap 2w CEP group: every morning up to two weeks. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
Analysis of the metabolic parameters by capillary sampling_CEPCap end CEP group: at the end of training sessions up to two weeks. Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy