A Non-randomized Pilot Study of the Impact on Rehabilitation Outcomes of a Course of Whole-body Cryostimulation (WBC) Treatment on Patients With Metabolic or Neurological Diseases or Fibromyalgia

Introduction: Istituto Auxologico Italiano (IAI) has as its institutional mission the study, treatment and rehabilitation of patients with obesity and neurological disorders as well as translational research from bench to bedside to improve these care pathways. The validation of innovative therapeutic modalities of proven efficacy on these patients, potentially scalable to the health care system, is a signature activity of the Institute's Current Research program. IAI in Piancavallo admits 3300 rehabilitation patients with comorbid obesity, including fibromyalgia, and 480 with neurological conditions each year. Pain, chronic fatigue, poor sleep quality, inflammatory status, thymic tone deflection, and obesity have a negative impact on rehabilitation treatment. Whole-body Cryostimulation (WBC) represents an innovative method that induces increased thermogenesis by promoting weight loss, reduced inflammation and oxidative stress with therapeutic effect on fatigue, pain, thymic tone and sleep (Polish Cryomedical Society, Polish Society for Rheumatology). 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. This would be reflected in increased tolerance to rehabilitation treatment, improved neuro-cognitive performance and psychological state. The metabolic effect of repeated cold exposure with WBC (browning of adipose tissue and increased thermogenesis) would allow, within multidisciplinary rehabilitation pathways, a better weight loss goal for functional recovery and disease progression in patients with obesity. Since the changes demonstrated at the molecular level after WBC are similar to those induced by exercise, WBC treatment would represent a potential alternative to exercise that is often poorly tolerated in patients with complicated metabolic diseases and disabling neurological conditions and thus a complementary innovative nonpharmacological rehabilitation strategy within a rehabilitation pathway.

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).

Anthropometric values, body composition, plasma catecholamine concentration, demographic and hematological analyses, muscle strength and functional values of both groups will be assessed at admission (PRE-T0) and at discharge (POST-T10), two weeks later, for both groups within the hospital facility. They will undergo 10 sessions of WBC over two weeks (1 treatment per day, Monday through Friday, before exercise classes and physical therapy). Skin temperatures will be recorded immediately before and after each WBC exposure. Description of the WBC session: Study participants will be exposed to extremely cold, dry air at -110°C for 2-3 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 patient's skin surface temperature at the neck, quadriceps, popliteal fossa, and calf will be measured before and after each treatment. 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).