Effect of Omega-3 LCPUFA Intervention on Learning, Cognition, Behaviour and Visual Processing.

Study Overview
=================
Brief Summary
-----------------
The brain is primarily developed in the third trimester of pregnancy, but continues maturing through the late twenties, especially the prefrontal cortex. Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) are important structural components of neural cell membranes, influence membrane fluidity and signal transduction, and thus learning, cognition and behaviour. Levels of omega-3 LCPUFA have been found to be low in individuals with limitations in these complex brain functions. Previous studies suggested that such functions could be improved by increasing LCPUFA. The adolescent brain, however, has been largely neglected. This study investigates the effect of one-year daily omega-3 LCPUFA supplementation, in particular krill oil, in healthy 14-15 year old adolescents in lower general secondary education (MAVO/VMBO) on learning, cognition, and behaviour. The majority of the omega-3 PUFA in krill oil is incorporated into phospholipids, favouring tissue uptake of its omega-3 PUFA. In a double blind, randomised controlled trial, 300 adolescents preselected from a population of 700 adolescents with low omega-3 index (<5%) will receive daily omega-3 LCPUFA supplementation or matching placebo. The omega-3 LCPUFA dose will be adjusted individually to reach a target level of 8-11%. The effects on learning (academic achievement, objective cognitive performance), behaviour (mood, self-esteem, motivation, goal-orientation, absenteeism), and in a subsample cognitive processes, in particular perceptual processes measured by eye-tracking will be evaluated after 6, 12, and 24 months. This study will yield important insights in the effects of omega-3 LCPUFA supplementation, a safe intervention, on a large variety of complex brain functions.

Official Title
-----------------
Food2Learn: Effect of Omega-3 LCPUFA Intervention on Learning, Cognition, Behaviour and Visual Processing.

Conditions
-----------------
Cognitive Function, Academic Performance, Mental Health

Intervention / Treatment
-----------------
* Dietary Supplement: Krill oil capsules
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adolescents aged 14-15 years. In lower general secondary education (MAVO/VMBO). Exclusion Criteria: Suffering from hemophilia (blood clotting disorder). Allergic to (shell)fish.

Ages Eligible for Study
-----------------
Minimum Age: 13 Years
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Krill oil capsules<br>Capsules containing krill oil rich in omega-3 fatty acid's. Dietary supplements (krill oil) are provided by Aker BioMarine Antarctic AS equalling almost the daily recommended amount of 450 mg of EPA/DHA intake per day. Addendum 25-4-2016: In the Original protocol a dose adjustment after 3 months according to Omega-3 Index was to be executed. As no participant achieved the target Omega-3 Index the dosage was adjusted to 800mg DHA + EPA per day for all participants. The also led to the decision to increase the starting dosage of cohort II to 800mg DHA+ EPA. | Dietary Supplement: Krill oil capsules<br>* 1 year supplementation with Krill oil provided by Aker BioMarine Antarctic AS equalling almost the daily recommended amount of 450 mg of EPA/DHA intake per day.<br>|
| Placebo Comparator: Placebo<br>Capsules containing a fatty acid mixture that reflects the fatty acid composition of the average European diet. | Dietary Supplement: Placebo<br>* Capsules containing a fatty acid mixture that reflects the fatty acid composition of the average European diet.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance | Neuropsychological tests covering seceral executive functions (LDST, D2, CST, Stroop, Digit Span). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye tracking | Two types of eye tracking parameters will be calculated, namely basic parameters and paragraph-related parameters. Basic parameters are number of blinks, number of fixations, total duration of fixations, average fixation duration, average dispersion of fixation positions, average saccadic amplitude, and average saccadic velocity. Moreover, we will calculate eye tracking measures per paragraph, namely time spent on each paragraph (number and duration of fixations), time elapsed until first looking at a paragraph, and amount of times going back to a paragraph (revisits). | 12 months | 
| Academic achievement | Grade point average for Dutch, English and mathematics and standardized mathematics test scores (AMN). | 12 months | 
| Behaviour: absenteeism, motivation (MSLQ), Mood (CES-D), Self-esteem | Absenteeism, motivation (MSLQ), Mood (CES-D), Self-esteem | 12 months | 
| Sleep duration and sleep quality | Sleep duration measured using ActivPAL and diary, Sleep quality determined using the adolescent sleep wake scale (ASWS) and the adolescent sleep hygiene scale (ASHS). | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Omega-3 fatty acids, Cognitive function, Academic performance, Mental health, Eye tracking, Krill oil, LCPUFA