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ZIMBA: Clinical Trial in Paediatric Obesity (ZIMBA)

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ClinicalTrials.gov Identifier: NCT03283813
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
Simonetta Bellone, Azienda Ospedaliero Universitaria Maggiore della Carita

Tracking Information
First Submitted Date  ICMJE September 13, 2017
First Posted Date  ICMJE September 14, 2017
Last Update Posted Date July 12, 2019
Actual Study Start Date  ICMJE February 5, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2017)
Change in HOMA-IR index [ Time Frame: Change from baseline HOMA-IR (V0) at 3 months (V1). ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03283813 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2017)
  • Change in glucose level during oral glucose tolerance test (OGTT) [ Time Frame: Change from Baseline OGTT (V0) at 3 months (V1) ]
    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.
  • Metabolic control: Improvement of metabolic risk factors [ Time Frame: Change from baseline lipid profile, insulin, leptin, adiponectin, GLP1 (V0) at 3 months (V1) ]
    Evaluate any variation of serum lipids, leptin, adiponectin, GLP1 and insulin during OGTT.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 13, 2017)
Change in inflammatory cytokines. [ Time Frame: Change from Baseline cytokines and metabolites (V0) at 3 months (V1). ]
Evaluate new cytokines and metabolites that regulates hormone metabolism.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE ZIMBA: Clinical Trial in Paediatric Obesity
Official Title  ICMJE Effects of a Supplementation With Zinc and Myo-inositol in Paediatric Obesity
Brief Summary

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.

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, 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Primary Purpose: Treatment
Condition  ICMJE
  • Obesity, Childhood
  • Insulin Resistance
  • Zinc Deficiency
  • Inositol
Intervention  ICMJE
  • Dietary Supplement: Zinc
    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)
  • Drug: Placebos
    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.
  • Drug: Myoinositol
    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)
Study Arms  ICMJE
  • Active Comparator: Active group - Zinc and Myo-inositol
    This arm will receive a supplementation with Zinc and Myo-inositol once a day.
    Interventions:
    • Dietary Supplement: Zinc
    • Drug: Myoinositol
  • Placebo Comparator: Placebo group
    This arm will receive a supplementation with a same product equal to the active product but without Zinc and Myo-inositol inside.
    Intervention: Drug: Placebos
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2017)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • both sexes
  • between 6 and 18 years of age
  • obese, according to the IOTF criteria (Cole TJ et al., 2000)
  • pubertal stage ≥ 3 according to the Tanner stage (Tanner et al., 1961)
  • HOMA-IR > 2,5 or insulin > 15 µU/ml
  • Serum Zinc level in the range of normality or under the normal levels.

Exclusion Criteria:

  • Adverse reactions to the product or component of the product (allergies…)
  • Genetic obesity (Prader Willi syndrome, Down syndrome), Metabolic obesity (Laurence-Biedl syndrome…), endocrinological obesity (Cushing syndrome, hypothyroidism)
  • Chronic diseases, hepatic or gastroenterological diseases
  • Medical treatment for chronic diseases
  • Supplementation with inositol-like products or supplements containing Zinc and Inositol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Simonetta Bellone, Assoc. Professor 0390321660693 simonetta.bellone@med.uniupo.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03283813
Other Study ID Numbers  ICMJE CE 99/17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Simonetta Bellone, Azienda Ospedaliero Universitaria Maggiore della Carita
Study Sponsor  ICMJE Azienda Ospedaliero Universitaria Maggiore della Carita
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Azienda Ospedaliero Universitaria Maggiore della Carita
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP