Catecholamine Response to Repeated Whole-Body Cryostimulation in Obesity

Study Overview
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Brief Summary
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The purpose of this study is twofold: firstly, to investigate the effects of 10 sessions of whole-body cryostimulation (WBC) at -110°C on blood catecholamine levels, and secondly, to investigate the effects of the sympathetic response on body composition, blood pressure, heart rate, lipid profile and physical performance. Thirty patients with obesity hospitalized for a 4-weeks rehabilitation program (diet + exercise) were non-randomly allocated either to a group undergoing the program or to a group receiving in addition ten 2-min WBC sessions at -110°C over two weeks.

Detailed Description
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Introduction: Catecholamine profile in the patient with obesity has been investigated, but a possible overdrive of the sympathetic system under both basal conditions and under different stimuli is still debated. A limited number of articles have suggested the possible use of whole-body cryostimulation (WBC) as an add-on treatment in the patient with obesity, with promising, though non conclusive, results. Exposure to cryogenic temperatures would cause activation of the sympathetic system and thus an increase in catecholamine levels, which would stimulate excess adipose tissue to convert from white, metabolically inert tissue to brown, i.e., metabolically active adipose tissue. In fact, it has been previously reported that repeated exposure to WBC reduces inflammation and oxidation, improving immunity, antioxidant activity, and insulin sensitivity, and increasing the percentage of brown adipose tissue (BAT) volume and fatty acid utilization by decreasing the percentage of adipose tissue. Participants: Using a consecutive sampling technique, the investigators will recruit patients for a comprehensive, multidisciplinary rehabilitation program for obesity. Patients of both sex, age 18-65 years with BMI > 35 kg/m2 will be selected and consecutively evaluated for inclusion in the protocol. Exclusion criteria are: severe psychiatric conditions, acute respiratory disease, acute cardiovascular disease, unstable hypertension, cold intolerance, claustrophobia, pregnancy, recent modification of usual drug treatment, previous treatment with WBC, weight loss in the last 3 months, and body temperature greater than 37.5°C. All patients will perform a multidisciplinary rehabilitation program (diet + exercise and physiotherapy). Study design: Patients will be assigned to either a rehabilitation + WBC (RWBC) or rehabilitation intervention (R) group in a consecutive, non-randomized manner until the total sample for each group is reached (15 subjects per group). All data were collected at baseline (PRE-T0) and after the experimental protocol (POST-T10). Blood samples for quantification of plasma catecholamine concentration were collected within 3 weeks, the day before the first WBC session and the day after the last. Anthropometric values, body composition, demographic and hematological analyses, muscle strength and functional values were collected within 4 weeks. Before the experiment, subjects assigned to RWBC were familiarized with WBC at T0. Then, they underwent 10 sessions of WBC over a 2-week period (1 treatment per day, Monday through Friday, at 8:15 a.m., before exercise classes and physical therapy). Skin temperatures were recorded within 1 minute before and after each WBC exposure. We then performed a comparison between the two treatment groups to assess the beneficial effects of WBC. Statistical analyses were performed on the total sample divided into the two groups. Description of the WBC session: Study participants will be exposed to extremely cold, dry air at -110°C for 2 minutes in a cryochamber (Artic, CryoScience, Rome. The first WBC session will last 1 minute at -110°C to familiarize the patient with the cryochamber temperature, while all subsequent treatments will last 2 minutes.The operator supervising the procedure will be in constant visual and vocal contact with the subjects. For safety reasons, the systolic and diastolic blood pressure of each participant will be measured before and after treatment. Rehabilitation program: The multidisciplinary rehabilitation program will consist of individual nutritional intervention, psychological support, and supervised physical activity throughout hospitalization. All patients will receive a balanced hypocaloric Mediterranean diet with 18-20 % proteins, 27-30 % fats (of which < 8% saturated fat) and 50-55 % carbohydrates (< 15% simple sugars), and 30 g of fibers from fresh vegetables. The diet plan will be organized by the hospital dietitian into three meals: breakfast, lunch, and dinner, with an energy distribution of 20 %, 40 % and 40 %, respectively. Two daily 60-minute physiotherapy sessions consisting of personalized progressive aerobic training, postural control exercises and progressive strengthening exercises were performed under the supervision of a physiotherapist. The first aerobic session performed in the morning after WBC consists of walking at a self-selected cadence. The second session performed in the afternoon consists of arm-cranking at an intensity of 65% of HRmax according to the Karvonen equation ((220 - age) × 0.65). Measurements. Demographic and clinical characteristics: Baseline demographic and clinical characteristics will be collected at the time of admission and will include age, sex, weight, height and body mass index (BMI). Body Composition: Body composition will be assessed in the morning in a quiet room at a temperature of 22-25 °C using bioimpedentiometry analyses with the patient in a supine position with lower limbs slightly apart and empty bladder. Whole-body resistance (Rz) and reactance (Xc) will be measured by trained operators. Skin temperatures: The patient's skin surface temperature at the neck,quadriceps, popliteal fossa, and calf will be measured before and within 1 min after each WBC treatment. Blood collection and Hematological/Biochemical analyses: Blood samples will be taken in the morning after overnight fasting conditions to determine plasma catecholamine levels. Performance-based physical functioning: To measure aerobic endurance, we will use the six-minute walk test (6MWT), performed indoors, along a 30-m, flat, undisturbed hospital corridor, with the length scored every 5 m. Chest pain, severe dyspnea, physical exhaustion, muscle cramps, sudden gait instability or other signs of severe distress are additional criteria for stopping the test. The Timed Up and Go test (TUG) test will be used to assess balance and functional mobility. The participant is asked to stand up from a standard chair, walk for 3 minutes, turn around, return to the chair, and sit down. The score corresponds to the time (seconds) taken to perform the test. Isometric strength will be assessed with the hand grip test using the American Society of Hand Therapists (ASHT) protocol as a reference. Statistical analysis: A sample of 15 obese adult individuals (BMI>35kg/m2, age 18-65 years, both sexes) will be considered for each of the two groups, for a total of 30 individuals. Since there is no a priori data on this and it is a pilot study, the sample size was chosen based on the literature, which suggests considering a minimum number of 12 subjects for pilot studies. To avoid confounding by BMI and age, patients will be matched for BMI and age to ensure an equal distribution between the groups of the variables believed to be confounding. Patients will not be blinded to study condition assignment.

Official Title
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A Non-randomized Pilot Study of Catecholamine Response to Repeated Whole-Body Cryostimulation in Patients With Severe Obesity

Conditions
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Obesity

Intervention / Treatment
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* Other: Whole-body cryostimulation (WBC)
* Other: Rehabilitation program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: both sexes age 18-65 yrs BMI > 35 kg/m2 Exclusion Criteria: severe psychiatric conditions acute respiratory disease acute cardiovascular disease unstable hypertension cold intolerance claustrophobia pregnancy recent modification of usual drug treatment previous treatment with WBC weight loss in the last 3 months body temperature greater than 37.5°C.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rehabilitation<br>Multidisciplinary rehabilitation program consisting of diet and physical exercise for 4 weeks. | Other: Rehabilitation program<br>* Multidisciplinary rehabilitation program consisting of diet and physical exercise.<br>* Other names: Multidisciplinary Rehabilitation program;|
| Experimental: Whole-Body Cryotherapy<br>Rehabilitation program consisting of 10 WBC sessions over two weeks. | Other: Whole-body cryostimulation (WBC)<br>* Multidisciplinary rehabilitation program consisting of 10 WBC sessions.<br>* Other names: Whole-body cryotherapy;Other: Rehabilitation program<br>* Multidisciplinary rehabilitation program consisting of diet and physical exercise.<br>* Other names: Multidisciplinary Rehabilitation program;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline blood catecholamine levels (epinephrine, norepinephrine and dopamine) | Catecholamine levels (ng/ml) in plasma samples will be measured at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skin temperatures after every session of WBC | The change in skin temperature of all body regions considered will be measured (nape of the neck, right quadriceps, right popliteal fossa, right calf) within 1 minute before and 1 minute after every session of WBC. | up to 1 minute | 
| Change from baseline biochemical blood parameters HDL, LDL, Triglycerides and Glucose | Analysis of blood biochemical parameters HDL, LDL, Triglycerides and Glucose (mg/dl) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline biochemical blood parameter HBA1C% | Analysis of HBA1C% at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline systolic blood pressure and diastolic blood pressure (mmHg) | Measurement of systolic blood pressure (PAS), diastolic blood pressure (PAD) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline heart rate (bpm) | Measurement of hear rate (HR) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline weight | Measurement of Weight (kg) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline BMI | Measurement of BMI (kg/m2) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline waist circumference | Measurement of waist circumference (cm) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline Fat Mass (FM), Free Fat Mass (FFM) and Muscle Mass (MM) | Measurement of FM, MM and FFM (kg) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline % of Fat Mass (FM), Free Fat Mass (FFM) and Muscle Mass (MM) | Measurement of FM, MM and FFM % at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline aerobic endurance | Measurement of aerobic endurance using the six-minute walk test (m) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline balance and functional mobility | Measurement of balance and functional mobility using the Timed Up and Go test (sec) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 
| Change from baseline isometric strength | Measurement of isometric strength using the hand grip test (kg) at baseline and two weeks later, after multidisciplinary rehabilitation (R group) or multidisciplinary rehabilitation + WBC (RWBC group). | up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Whole-Body cryostimulation, Rehabilitation, Catecholamines, Thermal stress