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NCT01576783

Omega Tots: A Randomized, Controlled Trial of Long-chain Polyunsaturated Fatty Acid Supplementation of Toddler Diets and Developmental Outcomes

Completed Phase 4 Results posted Last updated 29 June 2021
What this trial tests

Phase 4 trial testing Docosahexaenoic Acid + Arachidonic Acid (DHA+AA) in Preterm Birth in 377 participants. Completed in 6 April 2017.

Timeline
26 April 2012
Primary endpoint
6 April 2017
6 April 2017

Quick facts

Lead sponsorSarah Keim
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment377
Start date26 April 2012
Primary completion6 April 2017
Estimated completion6 April 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sarah Keim — full company profile →

Who can join

Adults 10 Months to 16 Months, any sex, with Preterm Birth or Child Development. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Erythrocyte Fatty Acid Levels Primary · Baseline to 180 days post-randomization

This outcome measure involved an examination of change in plasma and RBC fatty acid concentrations from the first study visit to the final study visit. The changes were calculated as the fatty acid level at 180 days minus the fatty acid level at baseline. Primary Outcome for 1st stage of project funded by Allen Foundation, Inc

Linoleic acid (18:2n-6)
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-2.1± 5.2
Placebo0.6± 4.4
Arachidonic acid (20:4n-6)
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid2.0± 2.6
Placebo-0.2± 1.1
Total n-6
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.2± 6.0
Placebo0.4± 5.0
α-linolenic acid (18:3n-3)
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.1± 0.4
Placebo0.0± 0.3
Eicosapentaenoic acid (20:5n-3)
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.0± 0.1
Placebo-0.1± 0.2
Docosapentaenoic acid (22:5n-3)
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.1± 0.1
Placebo0.0± 0.1
Docosahexaenoic acid (22:6n-3)
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid1.1± 1.0
Placebo-0.1± 0.2
Total n-3
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.9± 1.1
Placebo-0.2± 0.5
Erythrocyte Fatty Acid Levels (Additional Data) Primary · Baseline to 180 days post-randomization

This outcome measure involved an examination of change in plasma and RBC fatty acid concentrations from the first study visit to the final study visit. The changes were calculated as the fatty acid level at 180 days minus the fatty acid level at baseline. Primary Outcome for 1st stage of project funded by Allen Foundation, Inc

GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-3.2± 3.9
Placebo1.6± 2.8
Enrollment and Trial Completion Primary · Baseline to 180 days post-randomization

The number of children who enroll in the trial and the number of those children who return for study visits 2 and 3. Primary Outcome for 1st stage of project funded by Allen Foundation, Inc.

Study Visit 2 Completion
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid172
Placebo163
Study Visit 3 Completion
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid166
Placebo168
Adherence Primary · Baseline to 180 days post-randomization

The mean (average) percentage of packets consumed by the children assigned to the supplement or placebo. Primary Outcome for 1st stage of project funded by Allen Foundation, Inc

GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid80.6± 28
Placebo80.7± 25
(Behavior) Infant Behavior Questionnaire-Revised (IBQ-R; Short Form) Secondary · Baseline to 180 days post-randomization

Infant Behavior Questionnaire-Revised (IBQ-R; short form) was used to assess effortful control (12 items) and activity level (3 items). The IBQ-R measures early temperament-based inhibitory control,a key component of executive function as children mature. Scores range from 1 to 7, with higher scores indicating greater frequency of behaviors. IBQ-R scores were measured at baseline and then again at study completion (180 days post randomization). The scores were calculated as a change between two time points (the IBQ-R value at 180 days minus the IBQ-R value at baseline).

Effortful Control
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.7± 0.8
Placebo-0.5± 0.8
Activity Level
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.6± 1.5
Placebo0.5± 1.5
(Development) Bayley Scales of Infant and Toddler Development, Third Edition(Bayley-III) Secondary · Baseline to 180 days post-randomization

Bayley Scales of Infant and Toddler Development, third edition, (Bayley-III) is an instrument designed to measure the developmental functioning of infants and toddlers between the ages of 1 month and 42 months (age adjustments for prematurity are accommodated with the tool). It provides age specific composite scores for cognitive (91 items,score min 55 max 145), language (98 items, score min 47 max 153), and motor (138 items, score min 46 max 154) skills. For all scales, higher scores are better and lower scores indicate possible delay/deficit. Bayley-III scores were measured at baseline and t

Cognitive Composite
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-2.6± 13.3
Placebo-3.7± 12.2
Language Composite
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.5± 12.0
Placebo0.2± 12.6
Motor Composite
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.6± 12.5
Placebo-0.4± 12.7
Brief Infant Sleep Questionnaire (BISQ) Secondary · Baseline to 180 days post-randomization

The following sleep characteristics were captured based on caregiver-report: nocturnal sleep duration (hours), daytime sleep duration (hours), total sleep duration within a 24-hour period (hours). Larger values represent more time spent in each type of sleep. BISQ scores were measured at baseline and then again at study completion (180 days post randomization). The scores were calculated as a change between two time points (the BISQ value at 180 days minus the BISQ value at baseline).

Nocturnal Sleep Duration
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.25± 1.61
Placebo-0.16± 1.34
Daytime Sleep Duration
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.32± 1.15
Placebo-0.46± 1.25
Total Sleep Duration
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.07± 2.22
Placebo-0.57± 1.7
Body Composition Secondary · Baseline to 180 days post-randomization

Changes in body composition from baseline to 6 months post-randomization (weight, recumbent length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds). These measurements were converted to z scores for corrected age based on Child Growth Standards from the World Health Organization. The z-score indicates the number of standard deviations away from the mean. A z score of 0 is equal to the mean of a reference population (children the same age and sex). Values less than 0 indicate values lower than the reference population, while values greater than 0 indicate val

Weight
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.1± 0.4
Placebo0.0± 0.4
Recumbent Length
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.1± 0.9
Placebo0.2± 0.9
Head Circumference
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.0± 0.6
Placebo-0.1± 0.5
Mid-Upper Arm Circumference
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid0.0± 0.8
Placebo0.1± 0.7
Triceps Skinfold
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.0± 0.7
Placebo-0.1± 0.8
Subscapular Skinfold
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.2± 0.8
Placebo-0.2± 0.9
Brief Infant Toddler Social Emotional Assessment (BITSEA) Secondary · 180 days post-randomization

BITSEA measures socioemotional development in toddlerhood. Scores were summed to provide competence (range: 0-22) and problem (range: 0-62) scores, respectively. The problem scale is further divided into subscales: externalizing (6 items; range: 0-12), internalizing (8 items; range: 0-16), and dysregulation (8 items; range: 0-16). Additionally, 14 items comprise a red flag scale (range: 0-28). Eight items from the competence and nine items from the problem subscales are indicative of behaviors often seen in children with ASD. Each of the 17 ASD items was dichotomized to illustrate the presence

Competence
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid16.50± 3.09
Placebo16.73± 2.94
Problem
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid9.81± 6.01
Placebo10.18± 6.84
Externalizing
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid2.29± 2.06
Placebo2.30± 1.98
Internalizing
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid2.04± 1.58
Placebo2.31± 2.10
Dysregulation
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid3.25± 2.57
Placebo3.29± 2.59
Red Flag
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid2.93± 2.48
Placebo3.12± 2.85
ASD
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid4.11± 2.29
Placebo4.36± 2.98
Pervasive Developmental Disorders Screening Test - II, Stage 2 (PDDST-II) Secondary · 180 days post-randomization

The PDDST-II is a clinically derived, caregiver-completed screener to assist in differentiating an ASD diagnosis from other disorders in children with developmental concerns, including those born preterm. The PDDST-II comprised 14 yes/no items that indicate the presence (1) or absence (0) of developmental concerns. Items were summed (possible range: 0-14) and higher scores represented greater developmental concern.

GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid2.91± 2.35
Placebo3.37± 3.02
Other Long-term Outcomes: Sleep (BISQ) Secondary · Long-term effect (approximately 8 months) after intervention completion

Long-term (26-32 months of age) outcomes. This will be evaluated using scores on the Brief Infant Sleep Questionnaire (BISQ).The following sleep characteristics were captured based on caregiver-report: nocturnal sleep duration (hours), daytime sleep duration (hours), total sleep duration within a 24-hour period (hours). Larger values represent more time spent in each type of sleep. BISQ scores were measured at baseline and then again at post-intervention follow-up (approximately 8 months after the trial ended). The scores were calculated as a change between two time points (the BISQ value at p

Nocturnal Sleep Duration
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.11± 1.68
Placebo-0.38± 1.43
Daytime Sleep Duration
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.46± 1.30
Placebo-0.81± 1.41
Total Sleep Duration
GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid-0.57± 2.20
Placebo-1.17± 1.85
Other Long-term Outcomes: Sleep (CSHQ) Secondary · Long-term effect (approximately 8 months) after intervention completion

Long-term (26-32 months of age) outcomes. This will be evaluated using the total score on a subset of 13 items from the Children's Sleep Habits Questionnaire (CSHQ). The range in total score is 13-39. A higher score is indicative of more sleep problems.

GroupValue95% CI
Docosahexaenoic Acid + Arachidonic Acid18.82± 4.96
Placebo19.57± 5.40

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to 180 days post randomization. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Docosahexaenoic Acid + Arachidonic Acid
Serious: 0/189 (0%)
Deaths: 0/189
Placebo
Serious: 0/188 (0%)
Deaths: 0/188
Other adverse events (6 terms — click to expand)

ReactionSystemDocosahexaenoic Acid + Ara…Placebo
Gastrointestinal SymptomsGastrointestinal disorders
Misc SymptomsImmune system disorders
ENT SymptomsEar and labyrinth disorders
Respiratory symptomsRespiratory, thoracic and mediastinal disorders
Behavioral SymptomsSocial circumstances
Skin/Limb SymptomsSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT01576783 adverse events section.

Sponsor's own description

The purpose of this study is to examine whether supplementation with certain polyunsaturated fatty acids can help the cognitive development of children born preterm.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Effect of Docosahexaenoic Acid Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm: A Randomized Clinical Trial.
    Keim SA, Boone KM, Klebanoff MA, Turner AN, et al · · 2018 · cited 33× · PMID 30357263 · DOI 10.1001/jamapediatrics.2018.3082
  2. Gaps and Factors Related to Receipt of Care within a Medical Home for Toddlers Born Preterm.
    Boone KM, Nelin MA, Chisolm DJ, Keim SA. · · 2019 · cited 10× · PMID 30579584 · DOI 10.1016/j.jpeds.2018.10.065
  3. Docosahexaenoic Acid and Arachidonic Acid Supplementation and Sleep in Toddlers Born Preterm: Secondary Analysis of a Randomized Clinical Trial.
    Boone KM, Rausch J, Pelak G, Li R, et al · · 2019 · cited 9× · PMID 31538590 · DOI 10.5664/jcsm.7902
  4. Fatty Acid Supplementation and Socioemotional Outcomes: Secondary Analysis of a Randomized Trial.
    Boone KM, Parrott A, Rausch J, Yeates KO, et al · · 2020 · cited 8× · PMID 32887793 · DOI 10.1542/peds.2020-0284
  5. The timing and quality of sleep was associated with dietary quality and anthropometry in toddlers born preterm.
    Yisahak SF, Boone KM, Rausch J, Keim SA. · · 2023 · cited 4× · PMID 36905082 · DOI 10.1111/apa.16750
  6. Parental Perceptions and Behaviors Regarding Child Weight Status among Toddlers Born Preterm.
    Saleska JL, Sheppard K, Turner AN, Boone KM, et al · · 2020 · cited 4× · PMID 30919396 · DOI 10.1055/s-0039-1683959
  7. Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.
    Ingol TT, Li R, Boone KM, Rausch J, et al · · 2019 · cited 3× · PMID 31187863 · DOI 10.1093/jn/nxz115
  8. Docosahexaenoic and arachidonic acid supplementation at 1 year has mixed effects on development and behaviour at age 2 for preterm children.
    Boone KM, Pattison K, Pelak G, Sheppard KW, et al · · 2021 · cited 2× · PMID 33768637 · DOI 10.1111/apa.15858

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