ZIMBA: Clinical Trial in Paediatric Obesity

NCT03283813 | Completed Phase 4 DMC

• 1 other identifier: CE 99/17
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity, Childhood; Insulin Resistance; Zinc Deficiency; Inositol

Keywords

Paediatric Obesity; Insulin resistance; Zinc; Myo-inositol

Outcome Measures

Primary Outcomes (1)

• Change in HOMA-IR index

  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.

  Change from baseline HOMA-IR (V0) at 3 months (V1).

Secondary Outcomes (2)

• Change in glucose level during oral glucose tolerance test (OGTT)

  Change from Baseline OGTT (V0) at 3 months (V1)

• Metabolic control: Improvement of metabolic risk factors

  Change from baseline lipid profile, insulin, leptin, adiponectin, GLP1 (V0) at 3 months (V1)

Other Outcomes (1)

• Change in inflammatory cytokines.

  Change from Baseline cytokines and metabolites (V0) at 3 months (V1).

Study Arms (2)

Active group - Zinc and Myo-inositol

ACTIVE COMPARATOR

This arm will receive a supplementation with Zinc and Myo-inositol once a day.

Dietary Supplement: Zinc; Drug: Myoinositol

Placebo group

PLACEBO COMPARATOR

This arm will receive a supplementation with a same product equal to the active product but without Zinc and Myo-inositol inside.

Drug: Placebos

Interventions

Zinc DIETARY_SUPPLEMENT

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)

Active group - Zinc and Myo-inositol

Placebos DRUG

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.

Placebo group

Myoinositol DRUG

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)

Active group - Zinc and Myo-inositol

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliero Universitaria Maggiore della Carita: lead

Study Sites (1)

AOU Maggiore della Carità - Clinica Pediatrica - Ambulatorio di Auxologia ed Endocrinologia Pediatrica

Novara, 28100, Italy

Location

Related Publications (30)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 27688754 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. 1998 Apr;17(2):109-15. doi: 10.1080/07315724.1998.10718735.

  PMID: 9550453 BACKGROUND

• Garg VK, Gupta R, Goyal RK. Hypozincemia in diabetes mellitus. J Assoc Physicians India. 1994 Sep;42(9):720-1.

  PMID: 7883669 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Tanner JM. (1961). Growth at adolescence. 2 edn. Oxford: Blackwell Scientific Publications.

  BACKGROUND

• 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 BACKGROUND

• 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.

  BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Pediatric Obesity; Insulin Resistance

Interventions

Zinc; Inositol

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Professor

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 14, 2017
• Study Start: February 5, 2018
• Primary Completion: December 31, 2023
• Study Completion: March 10, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)