Clinical trial NCT05615883: Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients
Official title: Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Melanoma
Keywords: Primary Melanoma
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2022-11-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Pre/post intervention, two-arms, sequential study. Patients with newly diagnose of melanoma are eligible.The study will enroll a total of 20 patients (10 in the AEP and 10 in the CEP), who will be enrolled approximately in 12-13 months.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 final endpoint is to verify whether short-term physical exercise can represent a feasible and safe tool for re-setting antitumor immunity in early melanoma patients. Investigators will analyze how the acute physical exercise modifies systemic immunity and biochemical/metabolic parameters. Specifically, Investigators will verify whether the exercise will modify:1 the immunological profiling of blood including frequency and function of MDSC, together with the concomitant status of antitumor immunity; 2 blood concentration of biochemical and metabolic parameters related to physical exercise and immunity
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: before exercise session.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: at 24 post-exercise.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: at 72 hours post-exercise.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: CEP group: before exercise program.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: CEP group: after one week of exercise program.
measure: Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: CEP group: up to two weeks of exercise program.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: before exercise.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: after 40 minutes of exercise session
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: at 24 post-exercise.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: AEP group: at 72 hours post-exercise.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: CEP group: before exercise program.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: CEP group: after one week of exercise program.
measure: Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)
timeFrame: CEP group: up to two weeks of exercise program.
measure: Analysis of the "systemic metabolic milieu"_AEPMet before
timeFrame: AEP group: before exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPHor before
timeFrame: AEP group: before exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPInf before
timeFrame: AEP group: before exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPLip before
timeFrame: AEP group: before exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPcounts before
timeFrame: AEP group: before exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPMet 40
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPHor 40
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPInf 40
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPLip 40
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPcounts 40
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPMet 80
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPHor 80
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPInf 80
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPLip 80
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPcounts 80
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Analysis of the "systemic metabolic milieu"_AEPMet 24
timeFrame: AEP group: at 24 post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPHor 24
timeFrame: AEP group: at 24 post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPInf 24
timeFrame: AEP group: at 24 post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPLip 24
timeFrame: AEP group: at 24 post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPcounts 24
timeFrame: AEP group: at 24 post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPMet 72
timeFrame: AEP group: at 72 hours post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPHor 72
timeFrame: AEP group: at 72 hours post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPInf 72
timeFrame: AEP group: at 72 hours post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPLip 72
timeFrame: AEP group: at 72 hours post-exercise.
measure: Analysis of the "systemic metabolic milieu"_AEPcounts 72
timeFrame: AEP group: at 72 hours post-exercise.
measure: Analysis of the "systemic metabolic milieu"_CEPMet before
timeFrame: CEP group: before exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPHor before
timeFrame: CEP group: before exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPInf before
timeFrame: CEP group: before exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPLip before
timeFrame: CEP group: before exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEP counts before
timeFrame: CEP group: before exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPMet 1w
timeFrame: CEP group: after one week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPHor 1w
timeFrame: CEP group: after one week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPInf 1w
timeFrame: CEP group: after one week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPLip 1w
timeFrame: CEP group: after one week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPcounts 1w
timeFrame: CEP group: after one week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPMet 2w
timeFrame: CEP group: up to two week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPHor 2w
timeFrame: CEP group: up to two week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPInf 2w
timeFrame: CEP group: up to two week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPLip 2w
timeFrame: CEP group: up to two week of exercise program.
measure: Analysis of the "systemic metabolic milieu"_CEPcounts 2w
timeFrame: CEP group: up to two week of exercise program.
measure: Analysis of the metabolic parameters by capillary sampling_AEPCap before
timeFrame: AEP group: before exercise session.
measure: Analysis of the metabolic parameters by capillary sampling_AEPCap 40
timeFrame: AEP group: after 40 minutes of exercise session.
measure: Analysis of the metabolic parameters by capillary sampling_AEPCap 80
timeFrame: AEP group: after 80 minutes of exercise session.
measure: Analysis of the metabolic parameters by capillary sampling_AEPCap 24
timeFrame: AEP group: at 24 post-exercise.
measure: Analysis of the metabolic parameters by capillary sampling_AEPCap 72
timeFrame: AEP group: at 72 hours post-exercise.
measure: Analysis of the metabolic parameters by capillary sampling_CEPCap before
timeFrame: CEP group: during the first training session
measure: Analysis of the metabolic parameters by capillary sampling_CEPCap 2w
timeFrame: CEP group: every morning up to two weeks.
measure: Analysis of the metabolic parameters by capillary sampling_CEPCap end
timeFrame: CEP group: at the end of training sessions up to two weeks.
Secondary outcomes:
Other outcomes:
measure: Physical Activity Questionnaire
timeFrame: Within one month of the enrollment
measure: MeDiet questionnaire
timeFrame: Within one month of the enrollment
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
name: Licia Rivoltini, MD
role: PRINCIPAL_INVESTIGATOR
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