Catecholamine Response to Repeated Whole-Body Cryostimulation in Obesity
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional

Summary: 
      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: 
      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.
    

Intervention name(s): Whole-body cryostimulation (WBC); Rehabilitation program
Intervention type(s): Other; Other
Intervention description(s): Multidisciplinary rehabilitation program consisting of 10 WBC sessions.; Multidisciplinary rehabilitation program consisting of diet and physical exercise.
Other intervention name(s): Whole-body cryotherapy; Multidisciplinary Rehabilitation program
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Whole-Body cryostimulation; Obesity; Rehabilitation; Catecholamines; Thermal stress