GOOD-DAY Trial in Paediatric Obesity
Condition: Obesity, Childhood
MeSH terms: Obesity; Pediatric Obesity
Study type: Interventional

Summary: 
      Alongside efforts in public health and policy to reverse the childhood obesity epidemic,
      medical providers seek to play effective roles in prevention and treatment. Limited
      interventional studies with effective long-term maintenance of weight loss in children are
      available. Moreover, interventions should focus on modifying lifestyle, by improving also
      ludic educational training. In fact, the knowledge, attitudes, behaviors and skills developed
      through effective health programs may result in a better quality of life and empower children
      to make correct choices to promote the health of the individual the family and the community.
      For this reason, in a cohort of obese pediatric subjects with visceral adiposity, the aim of
      the study is to assess the efficacy of an educational training inspired to Mediterranean diet
      and based on gamification (as "The Mediterranean Goose") with respect to a conventional
      treatment on weight loss and improvement of cardio-metabolic risk factors.
    

Detailed description: 
      Study design: A single-center pilot open-label randomized control trial. Population: The
      study will comprise a total of 60 subjects of both sexes, between 10 and 18 years of age,
      obese, according to the IOTF criteria (Cole TJ et al., 2000) and with visceral adiposity, as
      waist circumference ≥ 90th percentile (Cook S et al., 2003 - Cruz ML, Goran MI, 2004 - de
      Ferranti SD et al., 2004), diet naïve or with failure of weight loss (defined as -1 kg/m2 BMI
      in 1 year).

      Inclusion/ Exclusion criteria (see Eligibility Criteria). Intervention: Patients will be
      randomized in a open-label, into two groups homogeneous for number and sex of the subjects.
      One group (group SD) will receive Standard Diet according to routine care and practice, and
      one group (group SD+MSD) will receive a standard diet according to routine clinical practice
      + a 30 minutes Mediterranean-Style Diet educational training with explanation of
      Mediterranean pyramid + gamification to Mediterranean diet inside the Hospital and at home
      throughout "The Mediterranean Goose".

      Dietary restriction: Thestandard diet will be distributed with 55-60% of carbohydrates
      (45-50% complex and no more than 10% refined and processed sugars), 25-30% lipids and 15%
      proteins, and will be performedin accordance with the calories of an isocaloric balanced diet
      calculated throughout the Italian LARN Guidelines for age and gender (Società Italiana di
      Nutrizione Umana, 2014), inspired to Mediterranean pyramid.The standard diet will be given as
      diet plans in writing, after explanation by a well-trained and experienced clinical
      paediatric endocrinologist.

      Education in Hospital: As well as receiving the aforementioned recommendations, the SD+MSD
      group will also receive a simple visual guide of Mediterranean food pyramid explained by a
      dietitian/nutritionist for 30 minutes (Bach-Faig A et al., 2011).

      Gamification: The MSD Group will be involved inside the Hospital in an educational and
      playful training playing to "The Mediterranean Goose" in the ludic area of the Pediatric
      Department; this game has been proposed in an educational project known as "Mediterranean
      diet and enhancement of traditional foodstuff - MedDiet", founded by European Union in the
      framework of the ENPI CBC Mediterranean Sea Basin Programme (www.med-diet.eu). This material
      will be given to the family for continue to play also at home.

      Physical activity: all subjects will receive general recommendations about performing
      physical activity. Exercise will be conducted daily and will consist of 30 minutes of aerobic
      physical activity.

      Randomization: Alternately per week, participants will be randomly assigned in a 1:1 to one
      of the two dietary intervention groups.

      Timing: Patients will be evaluated firstly at time of enrollment (V0) and, during the first 2
      weeks of study (V1), biochemical and ultrasound evaluations will be completed. During the
      year of intervention, patients will be evaluated after 3 months, 6 months and 12 months (V2,
      V3, V4).The following anthropometric measures, biochemical and ultrasound evaluations and
      questionnaires will be obtained:

        1. Anthropometric measures:

             -  height (V0, V2, V3, V4);

             -  weight (V0, V2, V3, V4);

             -  body mass index (BMI; Kg/m2) (V0, V2, V3, V4);

             -  waist and hip circumferences (V0, V2, V3, V4) for the calculation of the following
                ratios: waist/hip, waist/height;

             -  Tanner stage (V0, V2, V3, V4) (Tanner JM, 1961);

             -  blood pressure and heart rate (V0, V2, V3, V4).

        2. Biochemical evaluations (after a 12-h overnight fast): CBC with formula, serum
           insulin-like growth factor 1 (IGF1, ng/mL), 25-hydroxy (OH) vitamin D (ng/mL), uric acid
           (mg/dL), alkaline phosphatase (U/L), ACTH (pg/mL), cortisol (microg/dL), TSH (uuI/mL),
           fT4 (ng/dL) (V1, V3, V4); aspartate aminotransferase (AST, IU/L), alanine
           aminotransferase (ALT, IU/L); AST-to-ALT ratio will be calculated as the ratio of AST
           (IU/L) and ALT(IU/L)(V1, V3, V4); serum creatinine concentration (mg/dL) will be
           measured with the enzymatic method; according to the NKF-K/DOQI Guidelines for CKD in
           children and adolescents (Hogg RJ et al., 2003), the eGFR will be calculated using
           updated Schwartz's formula (Schwartz GJ et al., 2009): eGFR (mL/min/1.73 m2) = [0.413 x
           patient's height (cm)] / serum creatinine (mg/dL)(V1, V3, V4); glucose (mg/dL), insulin
           (μUI/mL); insulin-resistance (IR) will be calculated using the formula of Homeostasis
           Model Assessment (HOMA)-IR: (insulin [mU/L] x glucose [mmol/lL) / 22.5)(V1, V3, V4);
           lipid profile: total cholesterol (mg/dL), High-Density Lipoprotein (HDL)-cholesterol
           (mg/dL), triglycerides (mg/dL); Low-Density Lipoprotein (LDL)-cholesterol will be
           calculated by the Friedwald formula and non-HDL (nHDL)-cholesterol will be also
           calculated(V1, V3, V4); oral glucose tolerance test (OGTT: 1.75 g of glucose solution
           per kg, maximum 75 g) and samples willbe collected for the determination of glucose and
           insulin every 30 min. The area under the curve (AUC) for parameters after OGTT will be
           calculated according to the trapezoidal rule. Insulin sensitivity at fasting and during
           OGTT will be calculated as the formula of the Quantitative Insulin-Sensitivity Check
           Index (QUICKI) and Matsuda index (ISI). The stimulus for insulin secretion in the
           increment in plasma glucose as insulinogenic index will be calculated as the ratio of
           the changes in insulin and glucose concentration from 0 to 30 min (InsI). Βeta-cell
           compensatory capacity will be evaluated by the disposition index defined as the product
           of the ISI and InsI (DI) (Kahn SE et al., 1993)(V1, V4); a collection at rest of
           first-morning urine sample. Physical and chemical urinalysis; urine albumin (mg/L) will
           be determined by an advanced immunoturbidimetric assay and urine creatinine (mg/dL) will
           be measured using the enzymatic method. Urine albumin to creatinine ratio (u-ACR -
           mg/g), will be calculated using the following formula: [urine albumin (mg/dL) / urine
           creatinine (mg/dL)] x 1000. For these calculations both albumin and creatinine will be
           in the same unit. The subjects whose urine will be found positive, they will undergo a
           collection of two more samples and will be considered the u-ACR mean value of these (V1,
           V3, V4).

        3. Ultrasound evaluations:

             -  liver ultrasound(V1, V4);

             -  echocardiography and carotid sonography(V1, V4).

        4. Nutritional and physical activity measurements:

             -  KIDMED questionnaire for children and adolescents; the index comprises 16 yes or no
                questions (Serra-Majem L et al., 2004), and the total score of the KIDMED index
                ranged from -4 to 12 and is classified into 3 levels: 1)≥8: optimal Mediterranean
                diet; 2) 4-7: improvement is needed to adjust intake to the Mediterranean diet; 3)
                ≤3: very low diet quality; the Italian version is reported and approved by Istituto
                Superiore Sanità in Rapporti ISTISAN 12/42(Istituto Superiore della Sanità,
                Rapporti ISTISAN 12/42, 2012)(V0, V2, V3, V4);

             -  the Food Frequency Questionnaire section of the Children's Eating Habits
                Questionnaire (CEHQ-FFQ), performed by Identification and prevention of Dietary and
                lifestyle-induced health Effects In Children and infantS (IDEFICS) study, on which
                parents or other caregivers will be asked to report the number of meals the
                children usually consumed at home or at other people's homes, such as of
                grandparents and friends, in a typical week of the previous month (Huybrechts I et
                al., 2011) (V0, V2, V3, V4);

             -  24-hour recall and a list of all foods and constituents included in the Dietary
                Inflammatory Index (DII) along with the respective adjusted score will be
                evaluated. Food- and constituent-specific scores will be multiplied by the intake
                for each subject. and then will be summed to create the overall Inflammatory Index
                score (Cavicchia PP et al., 2009 - Shivappa N et al., 2014) (V0, V2, V3, V4);

             -  the Mediterranean Adequacy Index (MAI) will be obtained by dividing the sum of the
                percentage of total energy from typical Mediterranean food groups by the sum of the
                percentage of total energy from non-typical Mediterranean food groups, according to
                the following equation (Alberti-Fidanza A, Fidanza F, 2004) (V0, V2, V3, V4);

             -  the International Physical Activity Questionnaire (IPAQ) developed, validated for
                Italian adolescents (IPAQ-A) will be developed; It covers four domains of physical
                activity: (1) school-related physical activity, including activity during physical
                education classes and breaks, (2) transportation, (3) housework and (4) leisure
                time (Hagstromer M et al., 2008 - Mannocci A et al, Accepted to Minerva Pediatrica)
                (V0, V2, V3, V4).

      Outcomes (see Outcome Measures). Information retrieval: A case report form (CRF) will be
      completed for each subject included in the study. The source documents will be the hospital's
      or the physician's chart.

      Statistical e sample size: A sample of 60 individuals (30 in each group) has been estimated
      to be sufficient to demonstrate a difference of 0.4kg/m2 in BMISDS with a SD of 0.65 (Prodam
      F et al, 2013) with 90% power and a significance level of 95% and a drop-out rate of 20%
      using the Student test. Statistical significance will be assumed at P< 0.05. The statistical
      analysis will be performed with SPSS for Windows version 17.0 (SPSS Inc., Chicago, IL, USA).

      Organization characteristics: The study will be conducted at the Pediatric Endocrine Service
      of Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale,
      in Novara.

      All blood samples will be measured evaluated using standardized methods in the Hospital's
      Chemistry Laboratory, previously described (Prodam F et al., 2014 - Prodam F et al., 2016).

      Good Clinical Practice: The protocol will be conducted in accordance with the declaration of
      Helsinki. Informed consent will be obtained from all parents prior to the evaluations after
      careful explanations to each patient.
    

Intervention name(s): Mediterranean-Style Diet Educational Training
Intervention type(s): Behavioral
Intervention description(s): The intervention consists in a standard diet according to routine clinical practice + a 30 minutes Mediterranean-Style Diet educational training with explanation of Mediterranean pyramid + gamification to Mediterranean diet inside the Hospital and at home throughout "The Mediterranean Goose".
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Obesity; Paediatric; Mediterranean diet; Gamification; Insulin-resistance