Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder

Families and caregivers of children enrolled in the IAN Research between the age 5-8 and with an established diagnosis of autism will be invited to participate in the study by e-mail. All of these families have previously given consent to be contacted about research opportunities. Families who respond to the e-mail recruitment letter will undergo a brief screening process to determine if the child has any exclusion criteria and to ensure the child is age 5-8, has an autism spectrum disorder, and has elevated baseline levels of hyperactivity. Families will undergo an on-line informed consent process including assent of the child. All participants will be given an opportunity to speak with a study team member should they have any questions about the study or the informed consent process. Participants will sign the informed consent using an electronic signature, a process that has been used previously in the IAN network and approved by the John's Hopkins Institutional Review Board (IRB). Families meeting all eligibility criteria will be randomly assigned and mailed the study medication (omega-3 or placebo) which will be administered to children by the parents twice daily for six weeks. Both the study medication and the matching placebo are an orange-flavored pudding that is specifically designed to be palatable for young children. Assessment of child hyperactivity, social functioning, and overall disease severity will be measured at baseline, three and six weeks by the parents, who will complete on-line standard questionnaires; ABC, Social Responsiveness Scale (SRS), clinical Global Impressions Scale (CGI).

Side effects will be assessed every week by e-mail, and any report of a side effect will immediately be followed-up with telephone contact from the PI. Although omega-3 fatty acids are extremely safe in the prescribed doses, the PI or another study physician will still be on call 24-hours-a-day, 7-days-a-week to speak to participants about possible adverse events or new medical problems (all enrolled families are provided with this 24-hour emergency phone contact information).

As part of the weekly e-mail reminder, parents will also be asked to log the medication that was provided to their children each day of the previous week to measure medication adherence.

• Omega-3 Fatty Acids (Drug), also known as Omega-3, N-3 Fatty Acid: Omega-3 fatty acids will be delivered in orange-flavored pudding packets (Coromega®, Vista, CA). Each packet contains 650 mg of omega-3 fatty acids, 350mg of eicosapentanoic acid (EPA), 230mg of docosahexanoic acid (DHA) and 2,000 mg of fish oil 18/12, and will be given twice daily for a daily dose of 1.3 grams of omega-3 fatty acids (and 1.1 grams of DHA + EPA).
• Placebo (Other): Placebo packets will have same orange-flavored pudding as active Omega-3 fatty acids comparator with an identical appearance and taste, but will include safflower oil instead of the fish oil. One placebo packet will be given twice daily.

Primary outcomes

• Change in Aberrant Behavior Checklist - Hyperactivity Subscale (ABC-H) Score [Baseline, 6 weeks (3 week value to be collected)]: The Aberrant Behavior Checklist (ABC) is a 58-item survey. Items are rated on a 4-point scale from "0=no problem" to "3=major problem." Higher scores indicate greater severity. Scores can be computed for five subscales: hyperactivity, lethargy, stereotypical behavior, irritability, and inappropriate speech. The hyperactivity subscale is comprised of 16 items. The outcome measure is the change from baseline to 6 weeks. The total score ranges from 0 to 48.

Secondary outcomes

• Change in Aberrant Behavior Checklist - Lethargy Subscale Score [Baseline, Week 6]: The Aberrant Behavior Checklist (ABC) is a 58-item survey. Items are rated on a 4-point scale from "0=no problem" to "3=major problem." Higher scores indicate greater severity. Scores can be computed for five subscales: hyperactivity, lethargy, stereotypical behavior, irritability, and inappropriate speech. The lethargy subscale is comprised of 16 items. The outcome measure is the change from baseline to six weeks in the scale. Total score ranges from 0 to 48.
• Change in Aberrant Behavior Checklist - Stereotypy Subscale Score [Baseline, Week 6]: The Aberrant Behavior Checklist (ABC) is a 58-item survey. Items are rated on a 4-point scale from "0=no problem" to "3=major problem." Higher scores indicate greater severity. Scores can be computed for five subscales: hyperactivity, lethargy, stereotypical behavior, irritability, and inappropriate speech. The stereotypy subscale is comprised of 7 items. The outcome measure is the change from baseline to six weeks in the scale. Total score ranges from 0 to 21.
• Aberrant Behavior Checklist - Irritability Subscale Score [Baseline, Week 6]: The Aberrant Behavior Checklist (ABC) is a 58-item survey. Items are rated on a 4-point scale from "0=no problem" to "3=major problem." Higher scores indicate greater severity. Scores can be computed for five subscales: hyperactivity, lethargy, stereotypical behavior, irritability, and inappropriate speech. The irritability subscale is comprised of 15 items. The outcome measure is the change from baseline to six weeks in the scale. Total score ranges from 0 to 45.
• Aberrant Behavior Checklist - Inappropriate Speech Subscale Score [Baseline, Week 6]: The Aberrant Behavior Checklist (ABC) is a 58-item survey. Items are rated on a 4-point scale from "0=no problem" to "3=major problem." Higher scores indicate greater severity. Scores can be computed for five subscales: hyperactivity, lethargy, stereotypical behavior, irritability, and inappropriate speech. The inappropriate speech subscale is comprised of 4 items. The outcome measure is the change from baseline to six weeks in the scale. Total score ranges from 0 to 12.
• Change in Social Responsiveness Scale (SRS) Score [Baseline, Week 6]: Social interaction will be assessed with the SRS. This scale examines the presence and extent of autistic social impairment and is administered by parents or teachers of children with ASD. Higher scores are indicative of greater severity. Normative data have been derived from a sample of over 1,600 children. A total Total-score of 76 or higher is considered severe and strongly associated with a clinical diagnosis of Autistic Disorder. T-scores of 66 through 75 are interpreted as indicating Moderate deficiencies in reciprocal social behavior that are clinically significant and lead to substantial interference in everyday social interactions, whereas T-scores of 60 to 65 are in the Mild range and indicate mild to moderate deficits in social interaction. T scores of 59 and below are considered to be within typical limits and generally not associated with clinically significant ASD.
• Change in Clinical Global Impression - Improvement (CGI-I) Score [Baseline, Week 6]: Measures the clinical impression of improvement on a 7-point Likert scale (ranging from 1 - very much improved - to 7 - very much worse) is a commonly used measure of overall improvement in intervention studies of children with ASD. This tool will be completed by the parent and caregiver, and is therefore considered a modified version of the instrument, which is normally completed by a clinician. This is considered an exploratory analysis of this outcome tool since it is being used in a non-standard fashion. The number of participants who "responded" in each group is the number where the parents reported that their child was improved, much improved, or very much improved.

Sex: All, ages: 5 Years to 8 Years

Inclusion Criteria:

1. Children who are participating in Interactive Autism Network (IAN) Research Families
2. Diagnosis of (Autism Spectrum Disorders (ASD) by a professional and Social Communication Question (SCQ) score>12
3. Age 5-8
4. Aberrant Behavior Checklist - Hyperactivity subscale (ABC-H)>20

Exclusion Criteria:

1. Children in foster care and each parent must affirm that they are the biological or adoptive parent of the child
2. Allergy to fish
3. Bleeding disorder, current use of anticoagulant or anti-platelet therapy, or recent or planned surgery
4. Any major medical illness that interferes with regular school attendance
5. Current or recent (past six months) use of omega-3 fatty acid
6. Siblings with ASD

Participant flow

Outcome results

• Change in Aberrant Behavior Checklist - Hyperactivity Subscale (ABC-H) Score (Primary), Mean, units on a scale: Omega-3 -5.3 +/- 7.2; Placebo -3.4 +/- 7.5
• Change in Aberrant Behavior Checklist - Lethargy Subscale Score (Secondary), Mean, units on a scale: Omega-3 -2.1 +/- 4.2; Placebo 0.1 +/- 2.6
• Change in Aberrant Behavior Checklist - Stereotypy Subscale Score (Secondary), Mean, units on a scale: Omega-3 -2.0 +/- 3.7; Placebo -0.5 +/- 2.6
• Aberrant Behavior Checklist - Irritability Subscale Score (Secondary), Mean, units on a scale: Omega-3 -2.0 +/- 6.9; Placebo -2.1 +/- 4.4
• Aberrant Behavior Checklist - Inappropriate Speech Subscale Score (Secondary), Mean, units on a scale: Omega-3 -0.6 +/- 2.7; Placebo -0.9 +/- 2.2
• Change in Social Responsiveness Scale (SRS) Score (Secondary), Mean, Units on a scale: Omega-3 -2.6 +/- 8.3; Placebo -6.1 +/- 7.8
• Change in Clinical Global Impression - Improvement (CGI-I) Score (Secondary), Number, # parents reporting improvement: Omega-3 12; Placebo 10

Adverse events

Time frame: 6 weeks

Other adverse events by term

• Results publication: Bent S, Hendren RL, Zandi T, Law K, Choi JE, Widjaja F, Kalb L, Nestle J, Law P. Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. J Am Acad Child Adolesc Psychiatry. 2014 Jun;53(6):658-66. doi: 10.1016/j.jaac.2014.01.018. Epub 2014 Mar 12. PMID 24839884

• Paul A Law, M.D., Principal investigator, Kennedy Krieger Institute and Johns Hopkins University