Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients

Melanoma Clinical Trial

— Agility  

Official title:

Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05615883
• Other study ID #: INT 148/19
• Secondary ID: IG 2017 Project
• Status: Recruiting
• Phase: N/A
• Start date: January 20, 2020
• Est. completion date: March 31, 2023

Study information

• Verified date: September 2022
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: Licia Rivoltini, MD
• Phone: +3902/23903245
• Email: licia.rivoltini[@]istitutotumori.mi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 31, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Melanoma

Intervention

Other:
• AEP Group Walking Sessions
The AEP Program consists in a single walking session on a treadmill lasting 80 minutes
• CEP Group Walking Sessions
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.

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

References & Publications (33)

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Physical Activity Questionnaire	Patient's life style will be investigated using the short version of Physical Activity Questionnaire	Within one month of the enrollment
Other	MeDiet questionnaire	Patient's life style will be investigated using the short version of MeDiet questionnaire	Within one month of the enrollment
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	AEP group: before exercise session.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	AEP group: after 40 minutes of exercise session.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	AEP group: after 80 minutes of exercise session.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	AEP group: at 24 post-exercise.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	AEP group: at 72 hours post-exercise.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	CEP group: before exercise program.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	CEP group: after one week of exercise program.
Primary	Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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.	CEP group: up to two weeks of exercise program.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	AEP group: before exercise.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	AEP group: after 40 minutes of exercise session
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	AEP group: after 80 minutes of exercise session.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	AEP group: at 24 post-exercise.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	AEP group: at 72 hours post-exercise.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	CEP group: before exercise program.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	CEP group: after one week of exercise program.
Primary	Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)	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).	CEP group: up to two weeks of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_AEPMet before	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	AEP group: before exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPHor before	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	AEP group: before exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPInf before	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	AEP group: before exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPLip before	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	AEP group: before exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPcounts before	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	AEP group: before exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPMet 40	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	AEP group: after 40 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPHor 40	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	AEP group: after 40 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPInf 40	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	AEP group: after 40 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPLip 40	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	AEP group: after 40 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPcounts 40	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	AEP group: after 40 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPMet 80	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	AEP group: after 80 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPHor 80	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	AEP group: after 80 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPInf 80	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	AEP group: after 80 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPLip 80	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	AEP group: after 80 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPcounts 80	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	AEP group: after 80 minutes of exercise session.
Primary	Analysis of the "systemic metabolic milieu"_AEPMet 24	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	AEP group: at 24 post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPHor 24	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	AEP group: at 24 post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPInf 24	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	AEP group: at 24 post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPLip 24	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	AEP group: at 24 post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPcounts 24	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	AEP group: at 24 post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPMet 72	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	AEP group: at 72 hours post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPHor 72	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	AEP group: at 72 hours post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPInf 72	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	AEP group: at 72 hours post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPLip 72	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	AEP group: at 72 hours post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_AEPcounts 72	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	AEP group: at 72 hours post-exercise.
Primary	Analysis of the "systemic metabolic milieu"_CEPMet before	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	CEP group: before exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPHor before	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	CEP group: before exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPInf before	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	CEP group: before exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPLip before	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	CEP group: before exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEP counts before	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	CEP group: before exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPMet 1w	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	CEP group: after one week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPHor 1w	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	CEP group: after one week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPInf 1w	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	CEP group: after one week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPLip 1w	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	CEP group: after one week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPcounts 1w	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	CEP group: after one week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPMet 2w	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	CEP group: up to two week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPHor 2w	In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters	CEP group: up to two week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPInf 2w	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	CEP group: up to two week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPLip 2w	We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes	CEP group: up to two week of exercise program.
Primary	Analysis of the "systemic metabolic milieu"_CEPcounts 2w	Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.	CEP group: up to two week of exercise program.
Primary	Analysis of the metabolic parameters by capillary sampling_AEPCap before	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).	AEP group: before exercise session.
Primary	Analysis of the metabolic parameters by capillary sampling_AEPCap 40	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).	AEP group: after 40 minutes of exercise session.
Primary	Analysis of the metabolic parameters by capillary sampling_AEPCap 80	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).	AEP group: after 80 minutes of exercise session.
Primary	Analysis of the metabolic parameters by capillary sampling_AEPCap 24	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).	AEP group: at 24 post-exercise.
Primary	Analysis of the metabolic parameters by capillary sampling_AEPCap 72	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).	AEP group: at 72 hours post-exercise.
Primary	Analysis of the metabolic parameters by capillary sampling_CEPCap before	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).	CEP group: during the first training session
Primary	Analysis of the metabolic parameters by capillary sampling_CEPCap 2w	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).	CEP group: every morning up to two weeks.
Primary	Analysis of the metabolic parameters by capillary sampling_CEPCap end	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).	CEP group: at the end of training sessions up to two weeks.