APZinc: Weekly Zinc Chelate Supplementation on Children's Growth

• Sponsor: Federal University of São Paulo (Other)
• Overall Status: Completed
• CT.gov ID: NCT01911260
• Collaborator: (none)
• Enrollment: 199
• Arms: 4
• Duration (Months): 5.9

Study Details

Study Description

Brief Summary

The purpose of this study is to measure the effect of weekly zinc supplementation on schoolchildren with growth deficit or normal stature.

Condition or Disease	Intervention/Treatment	Phase
Short Stature	Dietary Supplement: Zinc amino acid chelate; Other: Placebo	Phase 2/Phase 3

Detailed Description

Zinc is an important micronutrient for humans. Trials with zinc have shown positive effects of supplementation on growth, but there is still a lack of results on schoolchildren population. This Randomized Double-Blind Controlled Trial was design to measure the effect of weekly zinc supplementation on schoolchildren with growth deficit and normal stature. Schoolchildren were allocated into two homogeneous groups named Growth Deficit (HAZ < -1,5 Z-score), and Normal Stature (HAZ between -1,0 and ±1,0 Z-score) and were randomly assigned to compose two exposed and two control groups to receive a supplement of 30mg of zinc amino acid chelate or placebo individually once a week, during 12 weeks. Children's heights were measured at the end of supplementation period and again after 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Effect of Weekly Zinc Chelate Supplementation on Schoolchildren's Growth: a Randomized Double-blind Controlled Trial
• Study Start Date: Sep 1, 2000
• Actual Primary Completion Date: Dec 1, 2000
• Actual Study Completion Date: Mar 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Growth Deficit+zinc amino acid chelate Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Dietary Supplement: Zinc amino acid chelate; During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
Placebo Comparator: Growth Deficit receiving placebo Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Other: Placebo; During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
Placebo Comparator: Normal Height receiving placebo For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Other: Placebo; During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
Active Comparator: Normal Height+zinc amino acid chelate For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Dietary Supplement: Zinc amino acid chelate; During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.

Outcome Measures

Primary Outcome Measures

1. Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period. [Height-for-Age Z-score was measured at the End of Supplementation period and again at the End of Follow-up period, with a 12 weeks interval.]

   Schoolchildren were allocated into two homogeneous groups named Growth Deficit (HAZ < -1,5 Z-score), and Normal Height (HAZ between -1,0 and ±1,0 Z-score), and were randomly assigned to compose two exposed groups to receive a supplement of 30mg of zinc amino acid chelate, and two control groups to receive placebo individually once a week, during 12 weeks. Children's heights were measured at the End of Supplementation period and again after 12 weeks (Follow-up period). In combination with sex and age we transformed stature to Height-for-Age, expressed in Z-score, which was calculated as a number of standard deviations or Z-scores below or above the reference mean or median value, according to the formula below: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population. We analyzed and discussed the change in HAZ (HAZ at the End of Follow-up period - HAZ at End of Supplementation).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). For the Normal Stature group(NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex.

Exclusion Criteria:

• Children of GD group were evaluated by a Pediatrician specialized in growth disorders with the objective of excluding any organic or genetic condition correlated with growth deficit.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Federal University of São Paulo

Investigators

• Study Director: José Augusto AC Taddei, MD, Dr PH, Federal University of São Paulo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ana Paula Poblacion, Master in Science, Federal University of São Paulo
• ClinicalTrials.gov Identifier: NCT01911260
• Other Study ID Numbers: APoblacionZinc
• First Posted: Jul 30, 2013
• Last Update Posted: Dec 24, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Ana Paula Poblacion, Master in Science, Federal University of São Paulo: Zinc; Growth; Child; Dietary Supplements; Randomized Controlled Trial
• Additional relevant MeSH terms: Dwarfism; Chelating Agents

Study Results

Participant Flow

Recruitment Details	From original database of 2.519 children, enrolled in the first and second grades of four State-run public basic schools, we selected this study sample using height for age indicator (HAZ). Meetings were held at school with parents/guardians to explain the objective and procedures of the study in order to obtain a written consent.
Pre-assignment Detail	From original database (n=2.519), we selected children with one and a half or more standard deviations below the mean height for age (HAZ) and gender of the reference population as Growth Deficit group. For the Normal Height group, HAZ was define as between -1 and +1 standard deviations from the mean height reference for age and sex (n=218).

Arm/Group Title	Growth Deficit+Zinc Amino Acid Chelate	Growth Deficit + Placebo	Normal Height+Zinc Amino Acid Chelate	Normal Height + Placebo
Arm/Group Description	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
Period Title: Supplementation Period
STARTED	50	50	49	50
COMPLETED	40	38	39	42
NOT COMPLETED	10	12	10	8
Period Title: Supplementation Period
STARTED	40	38	39	42
COMPLETED	27	18	24	30
NOT COMPLETED	13	20	15	12

Baseline Characteristics

Arm/Group Title	Growth Deficit+Zinc Amino Acid Chelate	Growth Deficit + Placebo	Normal Height+Zinc Amino Acid Chelate	Normal Height + Placebo	Total
Arm/Group Description	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Total of all reporting groups
Overall Participants	50	50	49	50	199
Age (Count of Participants)
<=18 years	50 100%	50 100%	49 100%	50 100%	199 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.63 (0.66)	7.64 (0.71)	7.63 (0.66)	7.64 (0.71)	7.63 (0.68)
Sex: Female, Male (Count of Participants)
Female	25 50%	25 50%	24 49%	25 50%	99 49.7%
Male	25 50%	25 50%	25 51%	25 50%	100 50.3%
Region of Enrollment (participants) [Number]
Brazil	50 100%	50 100%	49 100%	50 100%	199 100%

Outcome Measures

1. Primary Outcome

Title	Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period.
Description	Schoolchildren were allocated into two homogeneous groups named Growth Deficit (HAZ < -1,5 Z-score), and Normal Height (HAZ between -1,0 and ±1,0 Z-score), and were randomly assigned to compose two exposed groups to receive a supplement of 30mg of zinc amino acid chelate, and two control groups to receive placebo individually once a week, during 12 weeks. Children's heights were measured at the End of Supplementation period and again after 12 weeks (Follow-up period). In combination with sex and age we transformed stature to Height-for-Age, expressed in Z-score, which was calculated as a number of standard deviations or Z-scores below or above the reference mean or median value, according to the formula below: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population. We analyzed and discussed the change in HAZ (HAZ at the End of Follow-up period - HAZ at End of Supplementation).
Time Frame	Height-for-Age Z-score was measured at the End of Supplementation period and again at the End of Follow-up period, with a 12 weeks interval.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Deficit+Zinc Amino Acid Chelate	Growth Deficit + Placebo	Normal Height+Zinc Amino Acid Chelate	Normal Height + Placebo
Arm/Group Description	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.	For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
Measure Participants	27	18	24	30
Mean (Standard Deviation) [Z-Score]	0.04 (0.12)	-0.08 (0.45)	0.10 (0.15)	0.02 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Deficit+Zinc Amino Acid Chelate, Growth Deficit + Placebo
	Comments	Null Hypothesis: There isn't difference in the HAZ mean difference between children with Growth Deficit who received zinc amino acid or placebo. We attributed α=0.05, β=0.20, and power=0.80.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments	In intragroup of supplementation (zinc or placebo) we used the t-test for dependent samples in order to compare growth over time.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 2.0
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Height+Zinc Amino Acid Chelate, Normal Height + Placebo
	Comments	Null Hypothesis: There isn't difference in the HAZ mean difference between children with Normal Height who received zinc amino acid or placebo. We attributed α=0.05, β=0.20, and power=0.80.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments	In intragroup of supplementation (zinc or placebo) we used the t-test for dependent samples in order to compare growth over time.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 2.0
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected during 12 weeks.
Adverse Event Reporting Description	In the collection data spread sheet, there was a column for side effects (yes/no), and type of side effects (description given by the subject).
Arm/Group Title	Growth Deficit+Zinc Amino Acid Chelate		Growth Deficit Receiving Placebo		Normal Height+Zinc Amino Acid Chelate		Normal Height Receiving Placebo
Arm/Group Description	Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.		Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.		For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.		For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex. During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
All Cause Mortality
	Growth Deficit+Zinc Amino Acid Chelate		Growth Deficit Receiving Placebo		Normal Height+Zinc Amino Acid Chelate		Normal Height Receiving Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Growth Deficit+Zinc Amino Acid Chelate		Growth Deficit Receiving Placebo		Normal Height+Zinc Amino Acid Chelate		Normal Height Receiving Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)		0/49 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Growth Deficit+Zinc Amino Acid Chelate		Growth Deficit Receiving Placebo		Normal Height+Zinc Amino Acid Chelate		Normal Height Receiving Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/50 (4%)		0/50 (0%)		1/49 (2%)		0/50 (0%)
Gastrointestinal disorders
Gastrointestinal event	2/50 (4%)	2	0/50 (0%)	0	1/49 (2%)	1	0/50 (0%)	0

Limitations/Caveats

The sample loss is a factor that hinders the adoption of results as definitive. Even if they remained similar according to biodemographic variables, we cannot guarantee the maintenance of group equality defined in randomization.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.