Fatty Acid Supplementation in Children With ASD (Study 2)

Study Overview
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Brief Summary
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The objective of the protocol is to test the impact of Omega 3-6 on pre-specified biological signatures (IL-1β, IL-2, and IFNγ) and to correlate changes in the biological signatures with changes in ASD symptoms.

Detailed Description
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Children with ASD suffer from both mental and physical symptoms that affect quality of life and severely disrupt family well-being. The objective of the protocol is to test the impact of Omega 3-6 on pre-specified biological signatures (IL-1β, IL-2, and IFNγ) and to correlate changes in the biological signatures with changes in ASD symptoms. Fatty acid supplements are natural products with anti-inflammatory properties often used for treatment of ASD symptoms, but the efficacy remains unproven.

Official Title
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Fatty Acid Supplements Alter Biological Signatures and Behavior in Children With Autism Spectrum Disorder (ASD)

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: LCPUFA Oil Supplement
* Dietary Supplement: Canola Oil Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 2-6 years old ASD diagnosis at Nationwide Children's Hospital within the prior 6 months English is primary language Exclusion Criteria: Fatty acid supplementation in the past 6 months Consumes fatty fish more than 3 times per week Still breastfeeding or formula feeding Quadriparesis Deafness Blindness Seizure disorder diagnosis Autoimmune disorder including Type 1 Diabetes, Fragile X, Rett, Angelman Syndromes, Tuberous Sclerosis Feeding problems precluding consumption of the supplement Ingredient allergy (canola, fish, or borage seed) Planned surgeries scheduled within the time frame of trial participation

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Long chain polyunsaturated fatty acid (LCPUFA) Oil Supplement<br>25 mg/kg, 50 mg/kg, or 75 mg/kg of gamma-linoleic acid (GLA) + eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) as Omega 3-6 oil to be administered twice per day by mouth for 90 days | Drug: LCPUFA Oil Supplement<br>* 25 mg/kg, 50 mg/kg, or 75 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days<br>|
| Placebo Comparator: Canola Oil<br>Equal volume (25 mg/kg, 50 mg/kg, or 75 mg/kg) of placebo (canola) oil to be administered twice per day by mouth for 90 days | Dietary Supplement: Canola Oil Placebo<br>* Equal volume (25 mg/kg, 50 mg/kg, or 75 mg/kg) of placebo (canola) oil to be administered twice per day by mouth for 90 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pervasive Developmental Disorder Behavior Inventory (PDDBI) - Autism Composite | Change in PDDBI Autism Composite t-score. Autism Composite t-scores range from 0-100 (mean=50; SD=10). T scores ranging 40-60 are characteristic of most cases of autism. Higher scores indicate greater severity. T scores for the Social Approach Behaviors and Expressive Language domains are summed and subtracted from the sum of the T scores for the Sensory/Perceptual Approach Behaviors, Ritualisms/Resistance to Change, Social Pragmatic Problems, and Semantic/Pragmatic Problems domains to obtain the Autism Composite t-score. | Baseline to 90 days post randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vineland Adaptive Behavior Scales 2nd ed. (modified timeframe of 90 days) | Change in standard adaptive composite score, and communication and socialization subdomain scores. A standard score of <86 is an indication of low adaptive level (characteristic of children with autism)(lower scores indicate lower adaptive level). Mean=100, SD=15, range 20-160. | Baseline to 90 days post randomization. | 
| Pervasive Developmental Disorder (PDD) Behavior Inventory (PDDBI) - Aggressiveness Problems | Change in PDDBI Aggressiveness Problems t-score. Aggressiveness domain looks at self-directed aggressive behaviors, incongruous negative affect, problems when caregiver returns from an outing, aggressiveness towards others, and overall temperament problems. Aggressiveness t-scores range from 0-100 (mean 50; SD=10); higher scores are indicative of more aggressiveness. | Baseline to 90 days post randomization. | 
| Preschool Language Scales - 5 (PLS-5) | Changes in Auditory Comprehension, Expressive Communication, and Total Language Scale standard scores. Standard score range 50-150 (mean=100; SD=15). Higher scores represent better child comprehension of language and better ability to communicate with others. | Baseline to 90 days post randomization. | 
| Childhood Autism Rating Scale (CARS2) (2nd ed.) | Changes in Continuous Score. T-scores range 45-54 indicate average level of autism-related symptoms; T-scores >70 indicate extreme level of autism-related symptoms (higher scores indicate greater symptoms) | Baseline to 90 days post randomization. | 
| Autism Impact Measure | The Autism Impact Measure is a newly developed instrument for measuring change in ASD related behaviors. https://pubmed.ncbi.nlm.nih.gov/30968318/ Changes in ASD core symptoms based on the following subscales: Repetitive Behavior, Communication; Atypical Behavior; Social Reciprocity; Peer Interaction; Frequency; Impact. (established norms not yet available) Higher scores represent worse severity of ASD symptoms. | Baseline to 90 days post randomization. |