Clinical trial NCT06698588: Symptom-specific Effects of Omega-3 Across Neurodevelopmental Symptoms
Official title: Examining Symptom-Specific Effects of Omega-3 Fatty Acids in Children with ADHD / ASD Symptoms and Sleep Problems: a Network Approach.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sleep
Autism or Autistic Traits
ADHD or ADHD Traits
Keywords: Randomised Controlled Trial
Lead sponsor: Swansea University
Sponsor class: OTHER
First posted: 2024-11-21
Enrollment: 200
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Whilst we are conducting an RCT we are planning on taking a modern approach to data-analysis - time-varying network analysis. This approach moves beyond the traditional medical model and its diagnostic categories where the assumption is that symptoms stem from a common underlying cause, and treating that cause (via medication or therapy) should alleviate the symptoms. This approach has been largely unsuccessful.

In contrast, network analysis views mental health disorders as complex, interrelated systems of symptoms and does not lend itself to calculating composite of global scores (see project description for further information.
Primary purpose: TREATMENT

Brief summary: Our study aims to determine whether omega-3 fatty acid supplementation can improve sleep, mood, and behavior in children with sleep problems and symptoms of Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), or both. By using a transdiagnostic approach-focusing on specific symptoms rather than diagnostic labels-we aim to identify which children may benefit most from omega-3 supplementation, thereby enhancing inclusivity. Many previous studies have excluded children with both ASD and ADHD, or those without a formal diagnosis.

Detailed description: ASD and ADHD are highly diverse neurodevelopmental conditions with significant co-occurrence-some estimates suggest rates as high as 78% (Leitner, 2014). However, research often excludes neurodiverse children with co-occurring conditions or subclinical symptoms, making many study populations unrepresentative of real-world scenarios. Currently, there are no fully safe and effective treatments for ASD or ADHD symptoms (Groom \& Cortese, 2022; Oono et al., 2013; Williams et al., 2010), which leads many parents to explore complementary treatments, such as omega-3 supplements, among the most popular options (Green et al., 2006; Sinha \& Efron, 2005). Omega-3s, essential for brain development and function, are often deficient in UK children, particularly those with behavioral or learning difficulties (Montgomery et al., 2014).

Some clinical trials suggest that omega-3 supplementation, specifically EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), can improve symptoms such as sleep disturbances, hyperactivity-impulsivity, and inattention in children with ADHD and/or ASD-like difficulties (Bent et al., 2014; Richardson \& Montgomery, 2005). However, findings across studies have been inconsistent, with systematic reviews and meta-analyses yielding varied conclusions (Abdullah et al., 2019; Bloch \& Qawasmi, 2011; Gillies et al., 2012). These discrepancies likely arise from variations in study populations, treatments, outcome measures, and trial designs.

A key limitation is the traditional approach of treating ASD and ADHD as distinct diagnostic categories, adhering to the "latent variable" model in psychiatry, which assumes that symptoms reflect an underlying disorder. This approach has two major flaws: (a) it encourages studying groups presumed homogeneous based on diagnosis, ignoring within-group variability and symptom overlap across disorders, and (b) it directs treatment toward presumed underlying diseases rather than focusing on specific symptoms and their interactions. This "one-size-fits-all" model may contribute to the inconsistent findings in omega-3 research for neurodevelopmental conditions.

In contrast, network science offers a more dynamic approach, viewing disorders as networks of interacting symptoms rather than symptoms being caused by a single underlying disorder. This approach enables visualization of symptom networks, including complex connections that explain symptom overlap. For instance, "bridge" symptoms link different disorder domains, while "central" symptoms, which are highly connected, drive other symptoms and may be ideal treatment targets. Monitoring symptom networks during treatment can help identify individuals more likely to benefit based on unique symptom profiles (Bringmann et al., 2022; Bekhuis et al., 2018).

To date, the network approach has not been used to explore how omega-3 supplementation affects ASD and ADHD symptoms. Our study aims to apply this method to: (a) better understand the shared features of ADHD and ASD by identifying "bridge symptoms" and examining whether omega-3 supplementation influences these symptoms; (b) identify phenotypes that cross diagnostic boundaries and might benefit from omega-3 supplementation; and (c) promote a more inclusive approach to treating ADHD/ASD symptoms by focusing on symptom profiles rather than diagnostic labels.

We hypothesize that sleep disturbances and emotional dysregulation will act as "bridge nodes" that connect ADHD and ASD, given their presence across multiple disorders. Based on prior studies (Montgomery et al., 2014; Richardson, 2006; Richardson \& Montgomery, 2005), we also propose that omega-3 supplementation will directly improve a cluster of symptoms related to sleep, emotional regulation, and hyperactivity-impulsivity. Any additional benefits are expected to be indirect, resulting from improvements in these key symptoms.

Eligibility criteria: Inclusion Criteria:

Autism Spectrum Quotient 10 score \>5 OR Conners 3 Handscored Short Parent Form T score \> 64 for either the inattention OR hyperactivity subscales OR Children Sleep Habits Questionnaire SF score \>30 Able to swallow capsules

Exclusion Criteria:

Any major psychiatric condition likely to require hospitalization (e.g., Psychotic Disorders; Eating Disorders), but NB: for representativeness of typical children with ADHD/ASD, diagnosed mood/anxiety/sleep or other neurodevelopmental disorders will not be exclusion criteria; Severe learning difficulties (e.g., Down syndrome) Any serious medical condition; (d) allergy to any ingredients of the intervention or related substances

Primary outcomes:
measure: Changes in the network structure of symptoms before and after intervention.
timeFrame: Baseline and after 12-weeks
Secondary outcomes:
measure: Autism Spectrum Quotient 10
timeFrame: Baseline and after 12-weeks
measure: Conners 3 Handscored Short Parent Forms
timeFrame: Baseline and after 12-weeks
measure: Childrens Sleep Habits Questionnaire - SF
timeFrame: Baseline and after 12-weeks
measure: Strengths and Difficulties Questionnaire
timeFrame: Baseline and after 12-weeks
measure: Griffith Empathy Scale
timeFrame: Baseline and after 12-weeks
measure: Child Mania Rating Scale Parent version
timeFrame: Baseline and after 12-weeks
measure: Moods and feelings Questionnaire - SF
timeFrame: Baseline and after 12-weeks
Other outcomes:
measure: Arrow flanker
timeFrame: Baseline and after 12-weeks
measure: Stop signal task
timeFrame: Baseline and after 12-weeks
Locations:
city: Swansea
country: United Kingdom
facility: FHMLS
Study officials:
References: