A Clinical Trial to Study the Impact of a Nutritional Beverage on Tests of Memory in Healthy Preschool Age Children

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02177942
• Collaborator: (none)
• Enrollment: 528
• Location: 1
• Arms: 2
• Actual Duration (Months): 11.4
• Patients Per Site Per Month: 46.4

Study Details

Study Description

Brief Summary

The effect of supplementation using both protein and multiple micronutrients in preschool age children on cognitive performance and growth is unknown. The study will compare the effect of combination of protein and multiple micronutrients on indicators of cognitive performance and growth in preschool age children. Cognitive performance and anthropometric assessments will be measured at baseline and at 6 months.

Condition or Disease	Intervention/Treatment	Phase
Cognition	Other: Test beverage powder (High Proteins and added micronutrients); Other: Control beverage powder (Low protein and no added micronutrients)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 528 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Double Blind Randomised Controlled Trial in Pre-school Age Children to Evaluate the Impact of a Nutritional Beverage Powder on Cognitive Performance Measures
• Actual Study Start Date: Jun 20, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test beverage powder 30 grams of cereal beverage powder with protein and added micronutrients will be made up to 100 mL drink using luke warm water. Subjects will be administered two doses of the drink (100 mL each) everyday	Other: Test beverage powder (High Proteins and added micronutrients); High protein and added Micronutrients at recommended dietary allowance levels
Active Comparator: Control beverage powder 30 grams of cereal beverage powder with low protein and no added micronutrients will be made up to 100 mL using luke warm water. Subjects will be administered two doses of the drink (100 mL each) everyday	Other: Control beverage powder (Low protein and no added micronutrients); Low protein and no added micronutrients

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Short Term Memory at 6 Months [Baseline and 6 months]

   Short term memory was measured using word order and number recall sub tests of Kaufman Assessment Battery for Children (KABC).In Number Recall, child was asked to repeat series of number in same sequence after making sure that child is paying attention.A score of 0 and 1 given for incorrect and correct response respectively. In Word Order,qualified site staff said series of words and child then pointed pictures of those words in same sequence.Later items (object cards with pictures) included an interference task in which child named colors after hearing the word. Each subtest score was the total of item scores, ranging from 0-31 for word order and 0-22 for number recall. The two subtest scores were standardized for each subject and visit (Z score), and short term memory was calculated as the average of the two standardized values where higher scores reflect better short term memory.

Secondary Outcome Measures

1. Change From Baseline in Weight at 6 Months [Baseline and 6 months]

   Weight was measured (single measurement) in standard clothing on weighing scale to the nearest 0.1kilograms(kg).

2. Change From Baseline in Height at 6 Months [Baseline and 6 months]

   Height was measured (single measurement) using a portable stadio-meter, with the participant standing bare-foot, to the nearest 0.1centimeters (cm).

3. Change From Baseline in Body Mass Index (BMI) at 6 Months [Baseline and 6 months]

   BMI for was obtained using the World Health Organization Anthroplus software version 1.0.2.

4. Change From Baseline in Triceps Skin Fold (TSF) at 6 Months [Baseline and 6 months]

   The TSF was measured in the midline of the posterior aspect of the arm, over the triceps muscle, at a level midway between the lateral projection of the acromion process of the scapula and the inferior margin of the olecranon process of the ulna. The right elbow is flexed at 90°and the midpoint between the acromion and the olecranon process is located and marked at the lateral side of the arm. The skinfold was then measured with the arm hanging loosely while standing. The triceps skinfold was picked up with the left thumb and index finger approximately 1cm proximal to the marked level and the tips calipers were applied to the skin-fold at the marked level. The triceps measurement was done (three measurements) using Holtain calipers to the nearest 0.2 millimeters (mm) and the average value was recorded.

5. Change From Baseline in Mid Upper Arm Circumference (MUAC) at 6 Months [Baseline and 6 months]

   The MUAC (single measurement) was measured midway between the acromion and the olecranon process, while the participant stands with the elbow flexed at 90. The circumference was measured with a fiber glass tape to the nearest 0.1 cm on the right hand.

6. Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 6 Months [Baseline and 6 months]

   Using the MUAC measurement and TSF measurement, the arm muscle AMA and AFA were calculated i.e. AMA (cm2) = (MUAC-(π*TSF))2/4 π and AFA (cm2) = (MUAC2/4π) - AMA

7. Number of Ill Days at 6 Months [Baseline upto 6 months]

   Number of ill days due to cold, cough and/or associated fever were recorded. The mean number of ill days due was analyzed at 6 months using Analysis of Variance (ANOVA).

8. Change From Baseline in Problem Solving at 6 Months [Baseline and 6 months]

   Test measured visual construction ability, understanding of spatial relationships and problem solving abilities. The child arranged flat shapes of various sizes and colors (items) to match a model or picture as instructed by the qualified staff. For items 1 to 2 (score 2 for success on first trial and 1 on second trial); items 3 to 10 (Score 1 for success and 0 for failure on first trial). The test continued till 3 consecutive scores of 0. The Raw score was the total of item score. Score range 0-29. Higher scores reflect better short term memory

Eligibility Criteria

Criteria

• Ages Eligible for Study: 36 Months to 65 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Consent: Demonstrates understanding of the study and willingness to participate as evidenced by subject's parents or legally authorised representative's voluntary written informed consent and has received a signed and dated copy of the informed consent form.

2. Compliance : Understands and is willing, able and likely to comply with all study procedures and restrictions

3. General Health : Good general and mental health with, in the opinion of the investigator

4. Child with BMI for age between <+1 standard deviation (SD) to > -2SD

Exclusion Criteria:

1. Children in Care (CiC): A child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.

2. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (lactose, wheat gluten, soy protein) or any of their stated ingredients.

3. Child with severe anaemia (Haemoglobin < 7 g/dl) as determined by the non invasive spectrophotometry results.

4. Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit.

5. Participation in any nutritional study or didactic nutrition education in the last 6 months of the screening visit

6. Current or relevant history of any serious, severe or unstable physical or psychiatric illness or any medical disorder that would make the subject unlikely to fully complete the study or any condition that presents undue risk from the study product or procedures in the opinion of the investigator.

7. Recent history (3 months) of serious infections, injuries and/ or surgeries. 7. Children consuming iron, calcium and/or other nutritional supplements and/ or health food drinks on a regular basis (more than 3 times a week, in the recommended dosage) in the last 1 month prior to screening visit.

8. Use of any prescription medications during the study period for more than or equal to two weeks.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Karamsad	Gujarat	India	388325

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline
• Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02177942
• Other Study ID Numbers: 202155; RH01722
• First Posted: Jun 30, 2014
• Last Update Posted: Apr 1, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Micronutrients; Trace Elements

Study Results

Participant Flow

Recruitment Details	Participants were recruited at one center in India.
Pre-assignment Detail	A total of 656 participants were screened out of which 528 were randomized to study treatments. 363 participants completed the study. Of the 165 randomized participants not completing the study, 152 withdrew consent, 10 participants violated the protocol, 2 participants were lost to follow up and 1 withdrew due to adverse event.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mililiters (mL) drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Period Title: Overall Study
STARTED	262	266
COMPLETED	185	178
NOT COMPLETED	77	88

Baseline Characteristics

Arm/Group Title	Test	Control	Total
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	Total of all reporting groups
Overall Participants	185	178	363
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.21 (0.607)	4.24 (0.646)	4.22 (0.626)
Sex: Female, Male (Count of Participants)
Female	83 44.9%	66 37.1%	149 41%
Male	102 55.1%	112 62.9%	214 59%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Short Term Memory at 6 Months
Description	Short term memory was measured using word order and number recall sub tests of Kaufman Assessment Battery for Children (KABC).In Number Recall, child was asked to repeat series of number in same sequence after making sure that child is paying attention.A score of 0 and 1 given for incorrect and correct response respectively. In Word Order,qualified site staff said series of words and child then pointed pictures of those words in same sequence.Later items (object cards with pictures) included an interference task in which child named colors after hearing the word. Each subtest score was the total of item scores, ranging from 0-31 for word order and 0-22 for number recall. The two subtest scores were standardized for each subject and visit (Z score), and short term memory was calculated as the average of the two standardized values where higher scores reflect better short term memory.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [Score on a scale]	-0.04 (0.926)	-0.01 (0.856)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6931
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is test treatment minus control treatment such that a positive difference favours the test treatment.

2. Secondary Outcome

Title	Change From Baseline in Weight at 6 Months
Description	Weight was measured (single measurement) in standard clothing on weighing scale to the nearest 0.1kilograms(kg).
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday
Measure Participants	185	178
Mean (Standard Deviation) [kg]	0.15 (0.436)	0.14 (0.454)

3. Secondary Outcome

Title	Change From Baseline in Height at 6 Months
Description	Height was measured (single measurement) using a portable stadio-meter, with the participant standing bare-foot, to the nearest 0.1centimeters (cm).
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [cm]	0.23 (0.442)	0.20 (0.368)

4. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI) at 6 Months
Description	BMI for was obtained using the World Health Organization Anthroplus software version 1.0.2.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [kg/m^2]	0.00 (0.584)	0.02 (0.634)

5. Secondary Outcome

Title	Change From Baseline in Triceps Skin Fold (TSF) at 6 Months
Description	The TSF was measured in the midline of the posterior aspect of the arm, over the triceps muscle, at a level midway between the lateral projection of the acromion process of the scapula and the inferior margin of the olecranon process of the ulna. The right elbow is flexed at 90°and the midpoint between the acromion and the olecranon process is located and marked at the lateral side of the arm. The skinfold was then measured with the arm hanging loosely while standing. The triceps skinfold was picked up with the left thumb and index finger approximately 1cm proximal to the marked level and the tips calipers were applied to the skin-fold at the marked level. The triceps measurement was done (three measurements) using Holtain calipers to the nearest 0.2 millimeters (mm) and the average value was recorded.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [mm]	-0.33 (1.810)	-0.33 (2.062)

6. Secondary Outcome

Title	Change From Baseline in Mid Upper Arm Circumference (MUAC) at 6 Months
Description	The MUAC (single measurement) was measured midway between the acromion and the olecranon process, while the participant stands with the elbow flexed at 90. The circumference was measured with a fiber glass tape to the nearest 0.1 cm on the right hand.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test Beverage Powder	Control Beverage Powder
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [cm]	0.55 (1.131)	0.57 (1.016)

7. Secondary Outcome

Title	Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 6 Months
Description	Using the MUAC measurement and TSF measurement, the arm muscle AMA and AFA were calculated i.e. AMA (cm2) = (MUAC-(π*TSF))2/4 π and AFA (cm2) = (MUAC2/4π) - AMA
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Change from Baseline at 6 months (AMA)	1.34 (2.770)	1.39 (2.509)
Change from Baseline at 6 months (AFA)	-0.01 (1.146)	0.00 (1.330)

8. Secondary Outcome

Title	Number of Ill Days at 6 Months
Description	Number of ill days due to cold, cough and/or associated fever were recorded. The mean number of ill days due was analyzed at 6 months using Analysis of Variance (ANOVA).
Time Frame	Baseline upto 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [Number of days]	5.94 (3.130)	7.45 (8.976)

9. Secondary Outcome

Title	Change From Baseline in Problem Solving at 6 Months
Description	Test measured visual construction ability, understanding of spatial relationships and problem solving abilities. The child arranged flat shapes of various sizes and colors (items) to match a model or picture as instructed by the qualified staff. For items 1 to 2 (score 2 for success on first trial and 1 on second trial); items 3 to 10 (Score 1 for success and 0 for failure on first trial). The test continued till 3 consecutive scores of 0. The Raw score was the total of item score. Score range 0-29. Higher scores reflect better short term memory
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who were administered at least one study treatment during the study and provided at least one post-baseline assessment of efficacy which was same as end of study (at 6 months). This analysis was conducted on ITT population.

Arm/Group Title	Test	Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.	30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
Measure Participants	185	178
Mean (Standard Deviation) [Score on a scale]	2.86 (2.924)	3.03 (2.813)

Adverse Events

Adverse Event Reporting Description	Safety population, defined as all participants who were randomized and administered at least one study treatment during the study. The population of analysis was safety population (N=524).
Arm/Group Title	Test		Control
Arm/Group Description	30 grams of cereal beverage powder with protein and added micronutrients was made up to 100 mL drink using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.		30 grams of cereal beverage powder with low protein and no added micronutrients was made up to 100 mL using luke warm water. Participants were administered two doses of the drink (100 mL each) everyday.
All Cause Mortality
	Test		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Test		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/259 (0%)		3/265 (1.1%)
Infections and infestations
ACUTE GASTRO ENTERITIS	0/259 (0%)	0	1/265 (0.4%)	1
Nervous system disorders
CONVULSION	0/259 (0%)	0	1/265 (0.4%)	1
STATUS EPILAPTICUS	0/259 (0%)	0	1/265 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Test		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/259 (11.6%)		33/265 (12.5%)
Gastrointestinal disorders
VOMITING	6/259 (2.3%)	6	6/265 (2.3%)	6
DIARRHOEA	3/259 (1.2%)	3	3/265 (1.1%)	3
General disorders
PYREXIA	3/259 (1.2%)	3	8/265 (3%)	8
Infections and infestations
NASOPHARYNGITIS	9/259 (3.5%)	9	10/265 (3.8%)	10
UPPER RESPIRATORY TRACT INFECTION	7/259 (2.7%)	7	10/265 (3.8%)	10
PYODERMA	1/259 (0.4%)	1	0/265 (0%)	0
VARICELLA	1/259 (0.4%)	1	1/265 (0.4%)	1
GASTROENTERITIS	0/259 (0%)	0	3/265 (1.1%)	3
IMPETIGO	0/259 (0%)	0	1/265 (0.4%)	1
TYPHOID FEVER	0/259 (0%)	0	1/265 (0.4%)	1
NAUSEA	0/259 (0%)	0	1/265 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	3/259 (1.2%)	3	2/265 (0.8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.