Trial Outcomes & Findings for Vitamin B12, Neurodevelopment and Growth in Nepal (NCT NCT02272842)

Results Overview

Cognitive, Fine Motor, Gross Motor, Receptive language, and Expressive language scaled scores of the Bayley Scales of Infant Development version 3. This scale measures different aspects of neurodevelopment. The mean (SD) scores are usually 100 (15), and 95% of the population has scores between 70 and 130 (theoretical max/means 0/200). The higher scores, the better neurodevelopment; the scale is normalized on age.

Recruitment status

UNKNOWN

Study phase

PHASE2/PHASE3

Target enrollment

600 participants

Primary outcome timeframe

12 months

Results posted on

2023-09-18

Participant Flow

The enrollment commenced in April 2015 and ended in February 2017. All children were supplemented daily for one year. Follow-up ended in February 2018

Participant milestones

Participant milestones
Measure	Vitamin B12 A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Overall Study STARTED	300	300
Overall Study COMPLETED	284	290
Overall Study NOT COMPLETED	16	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Vitamin B12 A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Overall Study Lost to Follow-up	8	8
Overall Study Withdrawal by Subject	8	2

Baseline Characteristics

Vitamin B12, Neurodevelopment and Growth in Nepal

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vitamin B12 n=300 Participants A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=300 Participants A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.	Total n=600 Participants Total of all reporting groups
Age, Continuous	8.0 Months STANDARD_DEVIATION 1.8 • n=5 Participants	8.1 Months STANDARD_DEVIATION 1.8 • n=7 Participants	8.0 Months STANDARD_DEVIATION 1.8 • n=5 Participants
Sex: Female, Male Female	149 Participants n=5 Participants	142 Participants n=7 Participants	291 Participants n=5 Participants
Sex: Female, Male Male	151 Participants n=5 Participants	158 Participants n=7 Participants	309 Participants n=5 Participants
Race/Ethnicity, Customized Nepalese	300 Participants n=5 Participants	300 Participants n=7 Participants	600 Participants n=5 Participants
Length (cm)	65.837 cm STANDARD_DEVIATION 3.0 • n=5 Participants	65.94 cm STANDARD_DEVIATION 2.9 • n=7 Participants	65.9 cm STANDARD_DEVIATION 3.0 • n=5 Participants
Weight (kg)	7.3 kg STANDARD_DEVIATION 0.92 • n=5 Participants	7.3 kg STANDARD_DEVIATION 0.92 • n=7 Participants	7.3 kg STANDARD_DEVIATION .92 • n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Cognitive, Fine Motor, Gross Motor, Receptive language, and Expressive language scaled scores of the Bayley Scales of Infant Development version 3. This scale measures different aspects of neurodevelopment. The mean (SD) scores are usually 100 (15), and 95% of the population has scores between 70 and 130 (theoretical max/means 0/200). The higher scores, the better neurodevelopment; the scale is normalized on age.

Cognitive, Fine Motor, Gross Motor, Receptive language, and Expressive language scaled scores of the Bayley Scales of Infant Development version 3. This scale measures different aspects of neurodevelopment. The mean (SD) scores are usually 100 (15), and 95% of the population has scores between 70 and 130 (theoretical max/means 0/200). The higher scores, the better neurodevelopment; the scale is normalized on age.

Outcome measures

Outcome measures
Measure	Vitamin B12 n=289 Participants A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=283 Participants A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
The Bayley Scales of Infant Development Version 3 Cognitive	8.1 Scaled Scores Standard Deviation 1.6	8.2 Scaled Scores Standard Deviation 1.5
The Bayley Scales of Infant Development Version 3 Receptive language	9.0 Scaled Scores Standard Deviation 2.3	8.9 Scaled Scores Standard Deviation 2.5
The Bayley Scales of Infant Development Version 3 Expressive language	8.6 Scaled Scores Standard Deviation 2.6	8.5 Scaled Scores Standard Deviation 2.4
The Bayley Scales of Infant Development Version 3 Fine Motor	10.7 Scaled Scores Standard Deviation 1.6	10.9 Scaled Scores Standard Deviation 1.8
The Bayley Scales of Infant Development Version 3 Gross Motor	9.2 Scaled Scores Standard Deviation 2.0	9.1 Scaled Scores Standard Deviation 1.7

PRIMARY outcome

Timeframe: 12 months

Change in hemoglobin concentration from baseline to end study.

Outcome measures

Outcome measures
Measure	Vitamin B12 n=288 Participants A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=281 Participants A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Hemoglobin Concentration	1.1 g/dl Standard Deviation 1.1	1.0 g/dl Standard Deviation 1.2

SECONDARY outcome

Timeframe: 12 months

length and weight growth velocity z scores during supplementation z-scores, growth velocity. theoretical values -10 to 10 The higher the value, the faster the growth.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Using the collected data, identify morbidity, stimulation, nutrition, socioeconomic related predictors for neurodevelopment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Based on selected baseline variables we will identify subgroups who benefit from vitamin B12 supplementation

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Comparing mean plasma concentration of cobalamin between the study groups.

We will draw a blood sample at study start and at end study to measure to what extent vitamin status is altered.

Outcome measures

Outcome measures
Measure	Vitamin B12 n=277 Participants A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=286 Participants A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
The Effect of Vitamin B12 Supplementation on Markers of Vitamin B Status Cobalamin	316.3 mol/L Standard Deviation 1.7	290.1 mol/L Standard Deviation 1.6
The Effect of Vitamin B12 Supplementation on Markers of Vitamin B Status homocysteine'	6.6 mol/L Standard Deviation 1.3	8.2 mol/L Standard Deviation 1.4
The Effect of Vitamin B12 Supplementation on Markers of Vitamin B Status Methyl Malonic acid	0.3 mol/L Standard Deviation 1.9	.4 mol/L Standard Deviation 2.1

SECONDARY outcome

Timeframe: 12 months

We will measure to what extent vitamin B12 supplementation improves neurodevelopment measured by other tools such as the Ages and Stages Questionnaire (version 3) and the NEPSY II test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

We will investigate side effects such as pain, nausea, vomiting, regurgitation, allergic reactions and others after each dose of the intervention.

Outcome measures

Outcome measures
Measure	Vitamin B12 n=26 Participants A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=17 Participants A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Immediate Adverse Effects of the Intervention Urinary tract infections	3 Participants	0 Participants
Immediate Adverse Effects of the Intervention Lower respiratory infections	8 Participants	10 Participants
Immediate Adverse Effects of the Intervention Seizure related illness	7 Participants	2 Participants
Immediate Adverse Effects of the Intervention Constipation	1 Participants	1 Participants
Immediate Adverse Effects of the Intervention Other (surgical, diarrhea, sepsis, etc.)	7 Participants	4 Participants

SECONDARY outcome

Timeframe: 12 months

Relative leucocyte telomere length at end of the study period. Estimated by real-time PCR analysis

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Using actigraph and a structured questionaire on all children at baseline and at end of study measure the extent to which the intervention affects sleep.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 years

Population: All children who were available for assessment

Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition. This is a test of general abilities ("IQ-test") Expected mean (SD): 100 (15), higher value indicate better cognitive functioning. Range approx. 40-140

Outcome measures

Outcome measures
Measure	Vitamin B12 n=269 Participants A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=264 Participants A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Extended Followup: Neurodevelopment (IQ)	84.4 IQ points Standard Deviation 8.4	85.0 IQ points Standard Deviation 8.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

If funding allows, measure other markers related to neurodevelopment such as Brain Derived Neurotrophic Factor

Outcome measures

Outcome data not reported

Adverse Events

Vitamin B12

Serious events: 2 serious events

Other events: 70 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vitamin B12 n=300 participants at risk A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=300 participants at risk A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Infections and infestations Abscess	0.33% 1/300 • Number of events 1 • 1 year	0.00% 0/300 • 1 year
Skin and subcutaneous tissue disorders Burn	0.33% 1/300 • Number of events 1 • 1 year	0.00% 0/300 • 1 year

Other adverse events

Other adverse events
Measure	Vitamin B12 n=300 participants at risk A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India) Vitamin B12: Vitamin B12 in a multivitamin paste.	Placebo n=300 participants at risk A paste containing no vitamin B12 administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India) Placebo B12: Placebo B12 in a multivitamin paste.
Gastrointestinal disorders Regurgitation following paste administration.	23.3% 70/300 • Number of events 141 • 1 year	21.0% 63/300 • Number of events 134 • 1 year
Renal and urinary disorders Urinary tract infection	1.0% 3/300 • Number of events 3 • 1 year	0.00% 0/300 • 1 year
Respiratory, thoracic and mediastinal disorders Lower respiratory infection	2.0% 6/300 • Number of events 8 • 1 year	2.7% 8/300 • Number of events 10 • 1 year
Nervous system disorders Febrile seizures	2.0% 6/300 • Number of events 7 • 1 year	0.67% 2/300 • Number of events 2 • 1 year
Gastrointestinal disorders Constipation	0.33% 1/300 • Number of events 1 • 1 year	0.33% 1/300 • Number of events 1 • 1 year

Additional Information

Tor Strand

Innlandet Hospital Trust

Phone: +4790971086

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place