Cognition
Conditions
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.
Interventions
OTHERTest beverage powder (High Proteins and added micronutrients)
High protein and added Micronutrients at recommended dietary allowance levels
OTHERControl beverage powder (Low protein and no added micronutrients)
Low protein and no added micronutrients
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
36 Months to 65 Months
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 5\. 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. 6\. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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). |
| 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 |
| 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). |
| 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 |
| 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. |
Countries
India
Participant flow
Recruitment details
Participants were recruited at one center in India.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Test 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. | 185 |
| Control 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. | 178 |
| Total | 363 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 4 | 6 |
| Overall Study | Withdrawal by Subject | 71 | 81 |
Baseline characteristics
| Characteristic | Test | Control | Total |
|---|---|---|---|
| Age, Continuous | 4.21 Years STANDARD_DEVIATION 0.607 | 4.24 Years STANDARD_DEVIATION 0.646 | 4.22 Years STANDARD_DEVIATION 0.626 |
| Sex: Female, Male Female | 83 Participants | 66 Participants | 149 Participants |
| Sex: Female, Male Male | 102 Participants | 112 Participants | 214 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 259 | 33 / 265 |
| serious Total, serious adverse events | 0 / 259 | 3 / 265 |
Outcome results
Primary
Change From Baseline in Short Term Memory at 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.
Time frame: Baseline and 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Short Term Memory at 6 Months | -0.04 Score on a scale | Standard Deviation 0.926 |
| Control | Change From Baseline in Short Term Memory at 6 Months | -0.01 Score on a scale | Standard Deviation 0.856 |
p-value: 0.693195% CI: [-0.2, 0.13]ANCOVA
Secondary
Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 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
Time frame: Baseline and 6 months
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test | Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 6 Months | Change from Baseline at 6 months (AMA) | 1.34 Centimeter square Cm^2 | Standard Deviation 2.77 |
| Test | Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 6 Months | Change from Baseline at 6 months (AFA) | -0.01 Centimeter square Cm^2 | Standard Deviation 1.146 |
| Control | Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 6 Months | Change from Baseline at 6 months (AMA) | 1.39 Centimeter square Cm^2 | Standard Deviation 2.509 |
| Control | Change From Baseline in Arm Muscle Area (AMA) and Arm Fat Area (AFA) at 6 Months | Change from Baseline at 6 months (AFA) | 0.00 Centimeter square Cm^2 | Standard Deviation 1.33 |
Secondary
Change From Baseline in Body Mass Index (BMI) at 6 Months
BMI for was obtained using the World Health Organization Anthroplus software version 1.0.2.
Time frame: Baseline and 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Body Mass Index (BMI) at 6 Months | 0.00 kg/m^2 | Standard Deviation 0.584 |
| Control | Change From Baseline in Body Mass Index (BMI) at 6 Months | 0.02 kg/m^2 | Standard Deviation 0.634 |
Secondary
Change From Baseline in Height at 6 Months
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Height at 6 Months | 0.23 cm | Standard Deviation 0.442 |
| Control | Change From Baseline in Height at 6 Months | 0.20 cm | Standard Deviation 0.368 |
Secondary
Change From Baseline in Mid Upper Arm Circumference (MUAC) at 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.
Time frame: Baseline and 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Mid Upper Arm Circumference (MUAC) at 6 Months | 0.55 cm | Standard Deviation 1.131 |
| Control | Change From Baseline in Mid Upper Arm Circumference (MUAC) at 6 Months | 0.57 cm | Standard Deviation 1.016 |
Secondary
Change From Baseline in Problem Solving at 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
Time frame: Baseline and 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Problem Solving at 6 Months | 2.86 Score on a scale | Standard Deviation 2.924 |
| Control | Change From Baseline in Problem Solving at 6 Months | 3.03 Score on a scale | Standard Deviation 2.813 |
Secondary
Change From Baseline in Triceps Skin Fold (TSF) at 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.
Time frame: Baseline and 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Triceps Skin Fold (TSF) at 6 Months | -0.33 mm | Standard Deviation 1.81 |
| Control | Change From Baseline in Triceps Skin Fold (TSF) at 6 Months | -0.33 mm | Standard Deviation 2.062 |
Secondary
Change From Baseline in Weight at 6 Months
Weight was measured (single measurement) in standard clothing on weighing scale to the nearest 0.1kilograms(kg).
Time frame: Baseline and 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Change From Baseline in Weight at 6 Months | 0.15 kg | Standard Deviation 0.436 |
| Control | Change From Baseline in Weight at 6 Months | 0.14 kg | Standard Deviation 0.454 |
Secondary
Number of Ill Days at 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).
Time frame: Baseline upto 6 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Number of Ill Days at 6 Months | 5.94 Number of days | Standard Deviation 3.13 |
| Control | Number of Ill Days at 6 Months | 7.45 Number of days | Standard Deviation 8.976 |