Effects of a Supplementation With Zinc and Myo-inositol in Paediatric Obesity

ZIMBA: Clinical Trial in Paediatric Obesity



Sponsors


Source

Azienda Ospedaliero Universitaria Maggiore della Carita

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


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).

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 "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
(45-50% complex and no more than 10% refined and processed sugars), 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. Exercise will be conducted daily and will consist of 30 minutes of aerobic
physical activity.

Randomization: Participants will be randomly assigned in a 1:1 to active intervention Group
(Active Group, supplementation with Zinc and Myoinositol) 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 ) (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)(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
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)(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. 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 (V0, V1); 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; 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, 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, 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, V1);

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 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 prior to the evaluations after
careful explanations to each patient.

Overall Status

Not yet recruiting

Start Date

2017-10-01

Completion Date

2019-12-31

Primary Completion Date

2019-12-31

Phase

Phase 4

Study Type

Interventional

Primary Outcome

Measure

Time Frame

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

Secondary Outcome

Measure

Time Frame

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)

Enrollment

60

Conditions


Intervention

Intervention Type

Dietary Supplement

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)

Arm Group Label

Active group - Zinc and Myo-inositol


Intervention Type

Drug

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.

Arm Group Label

Placebo group



Eligibility

Criteria

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.

Gender

All

Minimum Age

6 Years

Maximum Age

18 Years

Healthy Volunteers

No


Overall Contact

Last Name

Simonetta Bellone, Assoc. Professor

Phone

0390321660693

Email



Location

Facility

Status

Contact

AOU Maggiore della Carità - Clinica Pediatrica - Ambulatorio di Auxologia ed Endocrinologia Pediatrica
Novara 28100 Italy
Not yet recruiting
Last Name: Simonetta Bellone, Professor
Phone: 0390321660693
Email: [email protected]

Location Countries

Country

Italy


Verification Date

2017-09-01

Lastchanged Date

2017-09-13

Firstreceived Date

2017-09-13

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Azienda Ospedaliero Universitaria Maggiore della Carita

Investigator Full Name

Simonetta Bellone

Investigator Title

Assoc. Professor


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Zinc

Inositol



Arm Group

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.



Firstreceived Results Date

N/A

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Acronym

ZIMBA

Other Outcome

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.


Firstreceived Results Disposition Date

N/A

Study Design Info

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.



ClinicalTrials.gov processed this data on September 14, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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