<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03283813</url>
  </required_header>
  <id_info>
    <org_study_id>CE 99/17</org_study_id>
    <nct_id>NCT03283813</nct_id>
  </id_info>
  <brief_title>ZIMBA: Clinical Trial in Paediatric Obesity</brief_title>
  <acronym>ZIMBA</acronym>
  <official_title>Effects of a Supplementation With Zinc and Myo-inositol in Paediatric Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero Universitaria Maggiore della Carita</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliero Universitaria Maggiore della Carita</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Myoinositol (MI) and D-chiro inositol (DCI) are isomeric forms of inositol that were found to&#xD;
      have insulin-like properties, acting as second messengers in the insulin intracellular&#xD;
      pathway; both of these molecules are involved in the increasing insulin sensitivity of&#xD;
      different tissues to improve metabolic and ovulatory functions. Myoinositol is the&#xD;
      predominant form that can be found in nature and food.&#xD;
&#xD;
      Inositol has been mainly used as a supplement in treating several pathologies such as&#xD;
      polycystic ovary syndrome (PCOS), metabolic syndrome, type 2 diabetes mellitus (T2DM) and&#xD;
      gestational diabetes (GDM). In the case of GDM, a condition defined as a glucose impairment&#xD;
      first detected in pregnancy, a preventive role of inositol for GDM onset was recognized. In&#xD;
      addition, inositol has been studied as a therapeutic option for the treatment of GDM and&#xD;
      T2DM. The main effect of inositol is decreasing the level of insulin resistance.&#xD;
      Consequently, a potential role of inositol as a treatment option could be hypothesized for&#xD;
      other conditions typically characterized by insulin resistance like metabolic syndrome and&#xD;
      obesity.&#xD;
&#xD;
      Zinc also plays an important role in insulin action and carbohydrate metabolism. It may also&#xD;
      have a protective role in the prevention of atherogenesis. Several human studies have&#xD;
      demonstrated that Zinc supplementation reduces total cholesterol, LDL cholesterol and&#xD;
      triglycerides, in addition to increasing the HDL cholesterol levels. Studies have shown that&#xD;
      diabetes is accompanied by hypozincemia and high levels of Zinc in urine. In addition Zinc is&#xD;
      also an integral part of key anti-oxidant enzymes and Zinc deficiency impairs their&#xD;
      synthesis, resulting in increased oxidative stress.&#xD;
&#xD;
      A supplementation with Myo-Inositol and Zinc could represent a valid strategy in paediatric&#xD;
      obesity in addiction to a standard approach. The purpose of our study is to evaluate the&#xD;
      supplementation of Myo-inositol and Zinc in the treatment of paediatric obesity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design: A single-center pilot open-label randomized control trial. Population: The&#xD;
      study will comprise a total of 60 subjects of both sexes, with pubertal stage ≥ 3 according&#xD;
      to the Tanner stage, obese according to the IOTF criteria (International Obesity Task Force),&#xD;
      diet naïve or with failure of weight loss (defined as -1 kg/m2 BMI in 1 year).&#xD;
&#xD;
      Intervention: Patients will be randomized in a open-label, into two groups homogeneous for&#xD;
      number and sex of the subjects. One group (group &quot;active&quot;) will receive the supplementation&#xD;
      with Myoinositol and Zinc (active product) and the other group (group &quot;Placebo&quot;) will receive&#xD;
      a placebo for a total of 3 months of treatment.&#xD;
&#xD;
      Dietary restriction: The standard diet will be distributed with 55-60% of carbohydrates,&#xD;
      25-30% lipids and 15% proteins, and will be performed in accordance with the calories of an&#xD;
      isocaloric balanced diet calculated throughout the Italian LARN Guidelines for age and gender&#xD;
      (Italian Society of Human Nutrition, 2014), inspired to Mediterranean pyramid.&#xD;
&#xD;
      Physical activity: all subjects will receive general recommendations about performing&#xD;
      physical activity.&#xD;
&#xD;
      Randomization: Participants will be randomly assigned in a 1:1 to active intervention Group&#xD;
      (Active Group) or Placebo Group.&#xD;
&#xD;
      Timing: Patients will be evaluated firstly at time of enrollment (V0) and at the end of the&#xD;
      end of the study (V1).&#xD;
&#xD;
      The following anthropometric measures, biochemical and ultrasound evaluations and&#xD;
      questionnaires will be obtained:&#xD;
&#xD;
        1. Anthropometric measures:&#xD;
&#xD;
             -  height (V0, V1);&#xD;
&#xD;
             -  weight (V0, V1);&#xD;
&#xD;
             -  body mass index (BMI; Kg/m2) (V0, V1);&#xD;
&#xD;
             -  waist and hip circumferences (V0, V1); for the calculation of the following ratios:&#xD;
                waist/hip, waist/height;&#xD;
&#xD;
             -  Tanner stage (V0, V1); (Tanner JM, 1961);&#xD;
&#xD;
             -  blood pressure and heart rate (V0, V1);&#xD;
&#xD;
        2. Biochemical evaluations (after a 12-h overnight fast): CBC (Complete Blood Count) with&#xD;
           formula, serum insulin-like growth factor 1 (IGF1, ng/mL), 25-hydroxy (OH) vitamin D&#xD;
           (ng/mL), uric acid (mg/dL), Serum Zinc (mg/dl), alkaline phosphatase (U/L), ACTH&#xD;
           (adrenocorticotropic hormone) (pg/mL), cortisol (microg/dL), TSH (thyroid-stimulating&#xD;
           hormone)(uuI/mL), fT4 (serum free T4) (ng/dL) (V0, V1); aspartate aminotransferase (AST,&#xD;
           IU/L), alanine aminotransferase (ALT, IU/L); AST-to-ALT ratio will be calculated as the&#xD;
           ratio of AST (IU/L) and ALT(IU/L) (V0, V1); serum creatinine concentration (mg/dL) will&#xD;
           be measured with the enzymatic method; according to the NKF-K/DOQI Guidelines for CKD in&#xD;
           children and adolescents (Dialysis Outcome Quality Initiative), the eGFR will be&#xD;
           calculated using updated Schwartz's formula: eGFR (mL/min/1.73 m2) = [0.413 x patient's&#xD;
           height (cm)] / serum creatinine (mg/dL)(V0, V1); glucose (mg/dL), insulin (μUI/mL);&#xD;
           insulin-resistance (IR) will be calculated using the formula of Homeostasis Model&#xD;
           Assessment (HOMA)-IR: (insulin [mU/L] x glucose [mmol/lL) / 22.5)(V0, V1); lipid&#xD;
           profile: total cholesterol (mg/dL), High-Density Lipoprotein (HDL)-cholesterol (mg/dL),&#xD;
           triglycerides (mg/dL); Low-Density Lipoprotein (LDL)-cholesterol will be calculated by&#xD;
           the Friedwald formula and non-HDL (nHDL)-cholesterol will be also calculated(V0, V1);&#xD;
           oral glucose tolerance test (OGTT: 1.75 g of glucose solution per kg, maximum 75 g) and&#xD;
           samples will be collected for the determination of glucose and insulin every 30 min. The&#xD;
           area under the curve (AUC) for parameters after OGTT will be calculated according to the&#xD;
           trapezoidal rule. Insulin sensitivity at fasting and during OGTT will be calculated as&#xD;
           the formula of the Quantitative Insulin-Sensitivity Check Index (QUICKI) and Matsuda&#xD;
           index (ISI). The insulinogenic index will be calculated as the ratio of the changes in&#xD;
           insulin and glucose concentration from 0 to 30 min (InsI). Βeta-cell compensatory&#xD;
           capacity will be evaluated by the disposition index defined as the product of the ISI&#xD;
           and InsI (DI) (V0, V1); a collection at rest of first-morning urine sample. Physical and&#xD;
           chemical urinalysis; urine albumin (mg/L) will be determined by an advanced&#xD;
           immunoturbidimetric assay and urine creatinine (mg/dL) will be measured using the&#xD;
           enzymatic method. Urine albumin to creatinine ratio (u-ACR - mg/g) (albumin-creatinine&#xD;
           ratio), will be calculated using the following formula: [urine albumin (mg/dL) / urine&#xD;
           creatinine (mg/dL)] x 1000. A sample of serum and a sample of plasma will be collected&#xD;
           at each time and will be stocked in -20°C freezer for further laboratory analysis (V0,&#xD;
           V1);&#xD;
&#xD;
        3. Nutritional and physical activity measurements:&#xD;
&#xD;
             -  KIDMED questionnaire for children and adolescents (Serra-Majem L et al., 2004). The&#xD;
                Italian version is reported and approved by Istituto Superiore Sanità in Rapporti&#xD;
                ISTISAN 12/42 (Istituto Superiore della Sanità, Rapporti ISTISAN 12/42, 2012)(V0,&#xD;
                V1);&#xD;
&#xD;
             -  the Food Frequency Questionnaire section of the Children's Eating Habits&#xD;
                Questionnaire (CEHQ-FFQ), performed by Identification and prevention of Dietary and&#xD;
                lifestyle-induced health Effects In Children and infantS (IDEFICS) study (V0, V1);&#xD;
&#xD;
      Information retrieval: A case report form (CRF) will be completed for each subject included&#xD;
      in the study. The source documents will be the hospital's or the physician's chart.&#xD;
&#xD;
      Statistical e sample size: A sample of 23 individuals has been estimated to be sufficient to&#xD;
      demonstrate a difference of 2 points of HOMA-IR (Prodam F et al, 2013) with 90% power and a&#xD;
      significance level of 95% and a drop-out rate of 10% using the Student test. Statistical&#xD;
      significance will be assumed at P&lt; 0.05. The statistical analysis will be performed with SPSS&#xD;
      for Windows version 17.0 (SPSS Inc., Chicago, IL, USA).&#xD;
&#xD;
      Organization characteristics: The study will be conducted at the Pediatric Endocrine Service&#xD;
      of Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale,&#xD;
      in Novara.&#xD;
&#xD;
      All blood samples will be measured evaluated using standardized methods in the Hospital's&#xD;
      Chemistry Laboratory, previously described (Prodam F et al., 2014 - Prodam F et al., 2016).&#xD;
&#xD;
      Good Clinical Practice: The protocol will be conducted in accordance with the declaration of&#xD;
      Helsinki. Informed consent will be obtained from all parents.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 5, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The study is a triple blind study in which the treatment or intervention is unknown to the research participant, the individuals who administer the treatment or intervention, and the researchers who assess the outcomes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HOMA-IR index</measure>
    <time_frame>Change from baseline HOMA-IR (V0) at 3 months (V1).</time_frame>
    <description>Evaluate if after the treatment with Myoinositol and Zinc supplementation there is a variation of HOMA-IR index.&#xD;
Evaluate if after the treatment with probiotic there is a variation of HOMA-IR index.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in glucose level during oral glucose tolerance test (OGTT)</measure>
    <time_frame>Change from Baseline OGTT (V0) at 3 months (V1)</time_frame>
    <description>Evaluate if after the treatment with Myoinositol and Zinc supplementation there is a reduction of glucose values during the OGTT at time 0' e 120' after oral glucose tolerance test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic control: Improvement of metabolic risk factors</measure>
    <time_frame>Change from baseline lipid profile, insulin, leptin, adiponectin, GLP1 (V0) at 3 months (V1)</time_frame>
    <description>Evaluate any variation of serum lipids, leptin, adiponectin, GLP1 and insulin during OGTT.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in inflammatory cytokines.</measure>
    <time_frame>Change from Baseline cytokines and metabolites (V0) at 3 months (V1).</time_frame>
    <description>Evaluate new cytokines and metabolites that regulates hormone metabolism.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Obesity, Childhood</condition>
  <condition>Insulin Resistance</condition>
  <condition>Zinc Deficiency</condition>
  <condition>Inositol</condition>
  <arm_group>
    <arm_group_label>Active group - Zinc and Myo-inositol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This arm will receive a supplementation with Zinc and Myo-inositol once a day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>This arm will receive a supplementation with a same product equal to the active product but without Zinc and Myo-inositol inside.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Zinc</intervention_name>
    <description>In this active Group there will be a supplementation with Zinc (5 mg), Myo-inositol (2000 mg) and GOS (Galacto-oligosaccharides) of Pisum sativum (1000 mg)</description>
    <arm_group_label>Active group - Zinc and Myo-inositol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>In this placebo Group there will be a supplementation with a product placebo equal to the active product with GOS (Galacto-oligosaccharides) of Pisum sativum(1000 mg) but without Zinc and Myo-inositol.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Myoinositol</intervention_name>
    <description>In this active Group there will be a supplementation with Zinc (5 mg), Myo-inositol (2000 mg) and GOS (Galacto-oligosaccharides) of Pisum sativum (1000 mg)</description>
    <arm_group_label>Active group - Zinc and Myo-inositol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  both sexes&#xD;
&#xD;
          -  between 6 and 18 years of age&#xD;
&#xD;
          -  obese, according to the IOTF criteria (Cole TJ et al., 2000)&#xD;
&#xD;
          -  pubertal stage ≥ 3 according to the Tanner stage (Tanner et al., 1961)&#xD;
&#xD;
          -  HOMA-IR &gt; 2,5 or insulin &gt; 15 µU/ml&#xD;
&#xD;
          -  Serum Zinc level in the range of normality or under the normal levels.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Adverse reactions to the product or component of the product (allergies…)&#xD;
&#xD;
          -  Genetic obesity (Prader Willi syndrome, Down syndrome), Metabolic obesity&#xD;
             (Laurence-Biedl syndrome…), endocrinological obesity (Cushing syndrome,&#xD;
             hypothyroidism)&#xD;
&#xD;
          -  Chronic diseases, hepatic or gastroenterological diseases&#xD;
&#xD;
          -  Medical treatment for chronic diseases&#xD;
&#xD;
          -  Supplementation with inositol-like products or supplements containing Zinc and&#xD;
             Inositol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Simonetta Bellone, Assoc. Professor</last_name>
    <phone>0390321660693</phone>
    <email>simonetta.bellone@med.uniupo.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>AOU Maggiore della Carità - Clinica Pediatrica - Ambulatorio di Auxologia ed Endocrinologia Pediatrica</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Simonetta Bellone, Professor</last_name>
      <phone>0390321660693</phone>
      <email>simonetta.bellone@med.uniupo.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013 Oct;95(10):1811-27. doi: 10.1016/j.biochi.2013.05.011. Epub 2013 Jun 10.</citation>
    <PMID>23764390</PMID>
  </reference>
  <reference>
    <citation>Larner J. D-chiro-inositol--its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47-60. doi: 10.1080/15604280212528.</citation>
    <PMID>11900279</PMID>
  </reference>
  <reference>
    <citation>Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008 Mar;24(3):139-44. doi: 10.1080/09513590801893232.</citation>
    <PMID>18335328</PMID>
  </reference>
  <reference>
    <citation>Muscogiuri G, Palomba S, Lagana AS, Orio F. Inositols in the Treatment of Insulin-Mediated Diseases. Int J Endocrinol. 2016;2016:3058393. doi: 10.1155/2016/3058393. Epub 2016 Sep 8. Erratum In: Int J Endocrinol. 2016;2016:6189820.</citation>
    <PMID>27688754</PMID>
  </reference>
  <reference>
    <citation>Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016;2016:1849162. doi: 10.1155/2016/1849162. Epub 2016 Oct 23.</citation>
    <PMID>27843451</PMID>
  </reference>
  <reference>
    <citation>Corrado F, D'Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, Di Benedetto A. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011 Aug;28(8):972-5. doi: 10.1111/j.1464-5491.2011.03284.x.</citation>
    <PMID>21414183</PMID>
  </reference>
  <reference>
    <citation>Pintaudi B, Di Vieste G, Bonomo M. The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes. Int J Endocrinol. 2016;2016:9132052. doi: 10.1155/2016/9132052. Epub 2016 Oct 11.</citation>
    <PMID>27807448</PMID>
  </reference>
  <reference>
    <citation>Mancini M, Andreassi A, Salvioni M, Pelliccione F, Mantellassi G, Banderali G. Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data. Int J Endocrinol. 2016;2016:8720342. doi: 10.1155/2016/8720342. Epub 2016 Nov 1.</citation>
    <PMID>27882052</PMID>
  </reference>
  <reference>
    <citation>Marreiro DN, Fisberg M, Cozzolino SM. Zinc nutritional status and its relationships with hyperinsulinemia in obese children and adolescents. Biol Trace Elem Res. 2004 Aug;100(2):137-49. doi: 10.1385/bter:100:2:137.</citation>
    <PMID>15326363</PMID>
  </reference>
  <reference>
    <citation>Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. 1998 Apr;17(2):109-15. doi: 10.1080/07315724.1998.10718735.</citation>
    <PMID>9550453</PMID>
  </reference>
  <reference>
    <citation>Garg VK, Gupta R, Goyal RK. Hypozincemia in diabetes mellitus. J Assoc Physicians India. 1994 Sep;42(9):720-1.</citation>
    <PMID>7883669</PMID>
  </reference>
  <reference>
    <citation>Ranasinghe P, Pigera S, Galappatthy P, Katulanda P, Constantine GR. Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications. Daru. 2015 Sep 17;23(1):44. doi: 10.1186/s40199-015-0127-4.</citation>
    <PMID>26381880</PMID>
  </reference>
  <reference>
    <citation>Islam MR, Arslan I, Attia J, McEvoy M, McElduff P, Basher A, Rahman W, Peel R, Akhter A, Akter S, Vashum KP, Milton AH. Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh. PLoS One. 2013 Apr 17;8(4):e61776. doi: 10.1371/journal.pone.0061776. Print 2013.</citation>
    <PMID>23613929</PMID>
  </reference>
  <reference>
    <citation>Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2012 Apr 19;4(1):13. doi: 10.1186/1758-5996-4-13.</citation>
    <PMID>22515411</PMID>
  </reference>
  <reference>
    <citation>Ranasinghe P, Wathurapatha WS, Ishara MH, Jayawardana R, Galappatthy P, Katulanda P, Constantine GR. Effects of Zinc supplementation on serum lipids: a systematic review and meta-analysis. Nutr Metab (Lond). 2015 Aug 4;12:26. doi: 10.1186/s12986-015-0023-4. eCollection 2015.</citation>
    <PMID>26244049</PMID>
  </reference>
  <reference>
    <citation>Kelishadi R, Hashemipour M, Adeli K, Tavakoli N, Movahedian-Attar A, Shapouri J, Poursafa P, Rouzbahani A. Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome. Metab Syndr Relat Disord. 2010 Dec;8(6):505-10. doi: 10.1089/met.2010.0020. Epub 2010 Oct 28.</citation>
    <PMID>21028969</PMID>
  </reference>
  <reference>
    <citation>Serra-Majem L, Ribas L, Ngo J, Ortega RM, Garcia A, Perez-Rodrigo C, Aranceta J. Food, youth and the Mediterranean diet in Spain. Development of KIDMED, Mediterranean Diet Quality Index in children and adolescents. Public Health Nutr. 2004 Oct;7(7):931-5. doi: 10.1079/phn2004556.</citation>
    <PMID>15482620</PMID>
  </reference>
  <reference>
    <citation>Huybrechts I, Bornhorst C, Pala V, Moreno LA, Barba G, Lissner L, Fraterman A, Veidebaum T, Hebestreit A, Sieri S, Ottevaere C, Tornaritis M, Molnar D, Ahrens W, De Henauw S; IDEFICS Consortium. Evaluation of the Children's Eating Habits Questionnaire used in the IDEFICS study by relating urinary calcium and potassium to milk consumption frequencies among European children. Int J Obes (Lond). 2011 Apr;35 Suppl 1:S69-78. doi: 10.1038/ijo.2011.37.</citation>
    <PMID>21483425</PMID>
  </reference>
  <reference>
    <citation>Prodam F, Ricotti R, Genoni G, Parlamento S, Petri A, Balossini C, Savastio S, Bona G, Bellone S. Comparison of two classifications of metabolic syndrome in the pediatric population and the impact of cholesterol. J Endocrinol Invest. 2013 Jul-Aug;36(7):466-73. doi: 10.3275/8768. Epub 2012 Nov 27.</citation>
    <PMID>23211535</PMID>
  </reference>
  <reference>
    <citation>Tanner JM. (1961). Growth at adolescence. 2 edn. Oxford: Blackwell Scientific Publications.</citation>
  </reference>
  <reference>
    <citation>Cole TJ, Lobstein T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes. 2012 Aug;7(4):284-94. doi: 10.1111/j.2047-6310.2012.00064.x. Epub 2012 Jun 19.</citation>
    <PMID>22715120</PMID>
  </reference>
  <reference>
    <citation>Società Italiana di Nutrizione Umana.(2014).Livelli di assunzione raccomandati di energia e nutrienti per la popolazione italiana (LARN). Milan, Italy: S.I.N.U.</citation>
  </reference>
  <reference>
    <citation>Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest. 2006 Jul-Aug;29(7):581-93. doi: 10.1007/BF03344156.</citation>
    <PMID>16957405</PMID>
  </reference>
  <reference>
    <citation>Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993 Nov;42(11):1663-72. doi: 10.2337/diab.42.11.1663.</citation>
    <PMID>8405710</PMID>
  </reference>
  <reference>
    <citation>Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS; National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. 2003 Jun;111(6 Pt 1):1416-21. doi: 10.1542/peds.111.6.1416.</citation>
    <PMID>12777562</PMID>
  </reference>
  <reference>
    <citation>Prodam F, Zanetta S, Ricotti R, Marolda A, Giglione E, Monzani A, Walker GE, Rampone S, Castagno M, Bellone S, Petri A, Aimaretti G, Bona G. Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity. J Pediatr. 2016 Apr;171:83-9.e1. doi: 10.1016/j.jpeds.2015.12.032. Epub 2016 Jan 12.</citation>
    <PMID>26794470</PMID>
  </reference>
  <reference>
    <citation>Prodam F, Savastio S, Genoni G, Babu D, Giordano M, Ricotti R, Aimaretti G, Bona G, Bellone S. Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height. PLoS One. 2014 Jan 30;9(1):e87157. doi: 10.1371/journal.pone.0087157. eCollection 2014.</citation>
    <PMID>24498035</PMID>
  </reference>
  <reference>
    <citation>Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med. 2003 Aug;157(8):821-7. doi: 10.1001/archpedi.157.8.821.</citation>
    <PMID>12912790</PMID>
  </reference>
  <reference>
    <citation>de Ferranti SD, Gauvreau K, Ludwig DS, Neufeld EJ, Newburger JW, Rifai N. Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey. Circulation. 2004 Oct 19;110(16):2494-7. doi: 10.1161/01.CIR.0000145117.40114.C7. Epub 2004 Oct 11.</citation>
    <PMID>15477412</PMID>
  </reference>
  <reference>
    <citation>Cruz ML, Goran MI. The metabolic syndrome in children and adolescents. Curr Diab Rep. 2004 Feb;4(1):53-62. doi: 10.1007/s11892-004-0012-x.</citation>
    <PMID>14764281</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>March 4, 2022</last_update_submitted>
  <last_update_submitted_qc>March 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliero Universitaria Maggiore della Carita</investigator_affiliation>
    <investigator_full_name>Simonetta Bellone</investigator_full_name>
    <investigator_title>Assoc. Professor</investigator_title>
  </responsible_party>
  <keyword>Paediatric Obesity</keyword>
  <keyword>Insulin resistance</keyword>
  <keyword>Zinc</keyword>
  <keyword>Myo-inositol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Pediatric Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inositol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03283813
org study id: CE 99/17
nct id: NCT03283813
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Myoinositol (MI) and D-chiro inositol (DCI) are isomeric forms of inositol that were found to
      have insulin-like properties, acting as second messengers in the insulin intracellular
      pathway; both of these molecules are involved in the increasing insulin sensitivity of
      different tissues to improve metabolic and ovulatory functions. Myoinositol is the
      predominant form that can be found in nature and food.

      Inositol has been mainly used as a supplement in treating several pathologies such as
      polycystic ovary syndrome (PCOS), metabolic syndrome, type 2 diabetes mellitus (T2DM) and
      gestational diabetes (GDM). In the case of GDM, a condition defined as a glucose impairment
      first detected in pregnancy, a preventive role of inositol for GDM onset was recognized. In
      addition, inositol has been studied as a therapeutic option for the treatment of GDM and
      T2DM. The main effect of inositol is decreasing the level of insulin resistance.
      Consequently, a potential role of inositol as a treatment option could be hypothesized for
      other conditions typically characterized by insulin resistance like metabolic syndrome and
      obesity.

      Zinc also plays an important role in insulin action and carbohydrate metabolism. It may also
      have a protective role in the prevention of atherogenesis. Several human studies have
      demonstrated that Zinc supplementation reduces total cholesterol, LDL cholesterol and
      triglycerides, in addition to increasing the HDL cholesterol levels. Studies have shown that
      diabetes is accompanied by hypozincemia and high levels of Zinc in urine. In addition Zinc is
      also an integral part of key anti-oxidant enzymes and Zinc deficiency impairs their
      synthesis, resulting in increased oxidative stress.

      A supplementation with Myo-Inositol and Zinc could represent a valid strategy in paediatric
      obesity in addiction to a standard approach. The purpose of our study is to evaluate the
      supplementation of Myo-inositol and Zinc in the treatment of paediatric obesity.
Study design: A single-center pilot open-label randomized control trial. Population: The
      study will comprise a total of 60 subjects of both sexes, with pubertal stage ≥ 3 according
      to the Tanner stage, obese according to the IOTF criteria (International Obesity Task Force),
      diet naïve or with failure of weight loss (defined as -1 kg/m2 BMI in 1 year).

      Intervention: Patients will be randomized in a open-label, into two groups homogeneous for
      number and sex of the subjects. One group (group "active") will receive the supplementation
      with Myoinositol and Zinc (active product) and the other group (group "Placebo") will receive
      a placebo for a total of 3 months of treatment.

      Dietary restriction: The standard diet will be distributed with 55-60% of carbohydrates,
      25-30% lipids and 15% proteins, and will be performed in accordance with the calories of an
      isocaloric balanced diet calculated throughout the Italian LARN Guidelines for age and gender
      (Italian Society of Human Nutrition, 2014), inspired to Mediterranean pyramid.

      Physical activity: all subjects will receive general recommendations about performing
      physical activity.

      Randomization: Participants will be randomly assigned in a 1:1 to active intervention Group
      (Active Group) or Placebo Group.

      Timing: Patients will be evaluated firstly at time of enrollment (V0) and at the end of the
      end of the study (V1).

      The following anthropometric measures, biochemical and ultrasound evaluations and
      questionnaires will be obtained:

        1. Anthropometric measures:

             -  height (V0, V1);

             -  weight (V0, V1);

             -  body mass index (BMI; Kg/m2) (V0, V1);

             -  waist and hip circumferences (V0, V1); for the calculation of the following ratios:
                waist/hip, waist/height;

             -  Tanner stage (V0, V1); (Tanner JM, 1961);

             -  blood pressure and heart rate (V0, V1);

        2. Biochemical evaluations (after a 12-h overnight fast): CBC (Complete Blood Count) with
           formula, serum insulin-like growth factor 1 (IGF1, ng/mL), 25-hydroxy (OH) vitamin D
           (ng/mL), uric acid (mg/dL), Serum Zinc (mg/dl), alkaline phosphatase (U/L), ACTH
           (adrenocorticotropic hormone) (pg/mL), cortisol (microg/dL), TSH (thyroid-stimulating
           hormone)(uuI/mL), fT4 (serum free T4) (ng/dL) (V0, V1); 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) (V0, V1); 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 (Dialysis Outcome Quality Initiative), the eGFR will be
           calculated using updated Schwartz's formula: eGFR (mL/min/1.73 m2) = [0.413 x patient's
           height (cm)] / serum creatinine (mg/dL)(V0, V1); 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)(V0, V1); 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(V0, V1);
           oral glucose tolerance test (OGTT: 1.75 g of glucose solution per kg, maximum 75 g) and
           samples will be 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 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) (V0, V1); 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) (albumin-creatinine
           ratio), will be calculated using the following formula: [urine albumin (mg/dL) / urine
           creatinine (mg/dL)] x 1000. A sample of serum and a sample of plasma will be collected
           at each time and will be stocked in -20°C freezer for further laboratory analysis (V0,
           V1);

        3. Nutritional and physical activity measurements:

             -  KIDMED questionnaire for children and adolescents (Serra-Majem L et al., 2004). 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,
                V1);

             -  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 (V0, V1);

      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 23 individuals has been estimated to be sufficient to
      demonstrate a difference of 2 points of HOMA-IR (Prodam F et al, 2013) with 90% power and a
      significance level of 95% and a drop-out rate of 10% 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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The study is a triple blind study in which the treatment or intervention is unknown to the research participant, the individuals who administer the treatment or intervention, and the researchers who assess the outcomes.
measure: Change in HOMA-IR index
time frame: Change from baseline HOMA-IR (V0) at 3 months (V1).
description: Evaluate if after the treatment with Myoinositol and Zinc supplementation there is a variation of HOMA-IR index.
Evaluate if after the treatment with probiotic there is a variation of HOMA-IR index.
measure: Change in glucose level during oral glucose tolerance test (OGTT)
time frame: Change from Baseline OGTT (V0) at 3 months (V1)
description: Evaluate if after the treatment with Myoinositol and Zinc supplementation there is a reduction of glucose values during the OGTT at time 0' e 120' after oral glucose tolerance test.
measure: Metabolic control: Improvement of metabolic risk factors
time frame: Change from baseline lipid profile, insulin, leptin, adiponectin, GLP1 (V0) at 3 months (V1)
description: Evaluate any variation of serum lipids, leptin, adiponectin, GLP1 and insulin during OGTT.
measure: Change in inflammatory cytokines.
time frame: Change from Baseline cytokines and metabolites (V0) at 3 months (V1).
description: Evaluate new cytokines and metabolites that regulates hormone metabolism.
arm group label: Active group - Zinc and Myo-inositol
arm group type: Active Comparator
description: This arm will receive a supplementation with Zinc and Myo-inositol once a day.
arm group label: Placebo group
arm group type: Placebo Comparator
description: This arm will receive a supplementation with a same product equal to the active product but without Zinc and Myo-inositol inside.
intervention type: Dietary Supplement
intervention name: Zinc
description: In this active Group there will be a supplementation with Zinc (5 mg), Myo-inositol (2000 mg) and GOS (Galacto-oligosaccharides) of Pisum sativum (1000 mg)
arm group label: Active group - Zinc and Myo-inositol
intervention type: Drug
intervention name: Placebos
description: In this placebo Group there will be a supplementation with a product placebo equal to the active product with GOS (Galacto-oligosaccharides) of Pisum sativum(1000 mg) but without Zinc and Myo-inositol.
arm group label: Placebo group
intervention type: Drug
intervention name: Myoinositol
description: In this active Group there will be a supplementation with Zinc (5 mg), Myo-inositol (2000 mg) and GOS (Galacto-oligosaccharides) of Pisum sativum (1000 mg)
arm group label: Active group - Zinc and Myo-inositol
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
last name: Simonetta Bellone, Assoc. Professor
phone: 0390321660693
email: simonetta.bellone@med.uniupo.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013 Oct;95(10):1811-27. doi: 10.1016/j.biochi.2013.05.011. Epub 2013 Jun 10.
PMID: 23764390
citation: Larner J. D-chiro-inositol--its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47-60. doi: 10.1080/15604280212528.
PMID: 11900279
citation: Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008 Mar;24(3):139-44. doi: 10.1080/09513590801893232.
PMID: 18335328
citation: Muscogiuri G, Palomba S, Lagana AS, Orio F. Inositols in the Treatment of Insulin-Mediated Diseases. Int J Endocrinol. 2016;2016:3058393. doi: 10.1155/2016/3058393. Epub 2016 Sep 8. Erratum In: Int J Endocrinol. 2016;2016:6189820.
PMID: 27688754
citation: Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016;2016:1849162. doi: 10.1155/2016/1849162. Epub 2016 Oct 23.
PMID: 27843451
citation: Corrado F, D'Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, Di Benedetto A. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011 Aug;28(8):972-5. doi: 10.1111/j.1464-5491.2011.03284.x.
PMID: 21414183
citation: Pintaudi B, Di Vieste G, Bonomo M. The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes. Int J Endocrinol. 2016;2016:9132052. doi: 10.1155/2016/9132052. Epub 2016 Oct 11.
PMID: 27807448
citation: Mancini M, Andreassi A, Salvioni M, Pelliccione F, Mantellassi G, Banderali G. Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data. Int J Endocrinol. 2016;2016:8720342. doi: 10.1155/2016/8720342. Epub 2016 Nov 1.
PMID: 27882052
citation: Marreiro DN, Fisberg M, Cozzolino SM. Zinc nutritional status and its relationships with hyperinsulinemia in obese children and adolescents. Biol Trace Elem Res. 2004 Aug;100(2):137-49. doi: 10.1385/bter:100:2:137.
PMID: 15326363
citation: Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. 1998 Apr;17(2):109-15. doi: 10.1080/07315724.1998.10718735.
PMID: 9550453
citation: Garg VK, Gupta R, Goyal RK. Hypozincemia in diabetes mellitus. J Assoc Physicians India. 1994 Sep;42(9):720-1.
PMID: 7883669
citation: Ranasinghe P, Pigera S, Galappatthy P, Katulanda P, Constantine GR. Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications. Daru. 2015 Sep 17;23(1):44. doi: 10.1186/s40199-015-0127-4.
PMID: 26381880
citation: Islam MR, Arslan I, Attia J, McEvoy M, McElduff P, Basher A, Rahman W, Peel R, Akhter A, Akter S, Vashum KP, Milton AH. Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh. PLoS One. 2013 Apr 17;8(4):e61776. doi: 10.1371/journal.pone.0061776. Print 2013.
PMID: 23613929
citation: Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2012 Apr 19;4(1):13. doi: 10.1186/1758-5996-4-13.
PMID: 22515411
citation: Ranasinghe P, Wathurapatha WS, Ishara MH, Jayawardana R, Galappatthy P, Katulanda P, Constantine GR. Effects of Zinc supplementation on serum lipids: a systematic review and meta-analysis. Nutr Metab (Lond). 2015 Aug 4;12:26. doi: 10.1186/s12986-015-0023-4. eCollection 2015.
PMID: 26244049
citation: Kelishadi R, Hashemipour M, Adeli K, Tavakoli N, Movahedian-Attar A, Shapouri J, Poursafa P, Rouzbahani A. Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome. Metab Syndr Relat Disord. 2010 Dec;8(6):505-10. doi: 10.1089/met.2010.0020. Epub 2010 Oct 28.
PMID: 21028969
citation: Serra-Majem L, Ribas L, Ngo J, Ortega RM, Garcia A, Perez-Rodrigo C, Aranceta J. Food, youth and the Mediterranean diet in Spain. Development of KIDMED, Mediterranean Diet Quality Index in children and adolescents. Public Health Nutr. 2004 Oct;7(7):931-5. doi: 10.1079/phn2004556.
PMID: 15482620
citation: Huybrechts I, Bornhorst C, Pala V, Moreno LA, Barba G, Lissner L, Fraterman A, Veidebaum T, Hebestreit A, Sieri S, Ottevaere C, Tornaritis M, Molnar D, Ahrens W, De Henauw S; IDEFICS Consortium. Evaluation of the Children's Eating Habits Questionnaire used in the IDEFICS study by relating urinary calcium and potassium to milk consumption frequencies among European children. Int J Obes (Lond). 2011 Apr;35 Suppl 1:S69-78. doi: 10.1038/ijo.2011.37.
PMID: 21483425
citation: Prodam F, Ricotti R, Genoni G, Parlamento S, Petri A, Balossini C, Savastio S, Bona G, Bellone S. Comparison of two classifications of metabolic syndrome in the pediatric population and the impact of cholesterol. J Endocrinol Invest. 2013 Jul-Aug;36(7):466-73. doi: 10.3275/8768. Epub 2012 Nov 27.
PMID: 23211535
citation: Tanner JM. (1961). Growth at adolescence. 2 edn. Oxford: Blackwell Scientific Publications.
citation: Cole TJ, Lobstein T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes. 2012 Aug;7(4):284-94. doi: 10.1111/j.2047-6310.2012.00064.x. Epub 2012 Jun 19.
PMID: 22715120
citation: Società Italiana di Nutrizione Umana.(2014).Livelli di assunzione raccomandati di energia e nutrienti per la popolazione italiana (LARN). Milan, Italy: S.I.N.U.
citation: Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest. 2006 Jul-Aug;29(7):581-93. doi: 10.1007/BF03344156.
PMID: 16957405
citation: Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993 Nov;42(11):1663-72. doi: 10.2337/diab.42.11.1663.
PMID: 8405710
citation: Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS; National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. 2003 Jun;111(6 Pt 1):1416-21. doi: 10.1542/peds.111.6.1416.
PMID: 12777562
citation: Prodam F, Zanetta S, Ricotti R, Marolda A, Giglione E, Monzani A, Walker GE, Rampone S, Castagno M, Bellone S, Petri A, Aimaretti G, Bona G. Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity. J Pediatr. 2016 Apr;171:83-9.e1. doi: 10.1016/j.jpeds.2015.12.032. Epub 2016 Jan 12.
PMID: 26794470
citation: Prodam F, Savastio S, Genoni G, Babu D, Giordano M, Ricotti R, Aimaretti G, Bona G, Bellone S. Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height. PLoS One. 2014 Jan 30;9(1):e87157. doi: 10.1371/journal.pone.0087157. eCollection 2014.
PMID: 24498035
citation: Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med. 2003 Aug;157(8):821-7. doi: 10.1001/archpedi.157.8.821.
PMID: 12912790
citation: de Ferranti SD, Gauvreau K, Ludwig DS, Neufeld EJ, Newburger JW, Rifai N. Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey. Circulation. 2004 Oct 19;110(16):2494-7. doi: 10.1161/01.CIR.0000145117.40114.C7. Epub 2004 Oct 11.
PMID: 15477412
citation: Cruz ML, Goran MI. The metabolic syndrome in children and adolescents. Curr Diab Rep. 2004 Feb;4(1):53-62. doi: 10.1007/s11892-004-0012-x.
PMID: 14764281
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliero Universitaria Maggiore della Carita
investigator full name: Simonetta Bellone
investigator title: Assoc. Professor
mesh term: Obesity
mesh term: Insulin Resistance
mesh term: Pediatric Obesity
mesh term: Inositol
sharing ipd: No