Autism Spectrum Disorder
Conditions
Brief summary
The purpose of this study is to examine how fatty acid supplementation alters biological signatures in children with ASD
Detailed description
Children with Autism Spectrum Disorder (ASD) suffer from both mental and physical symptoms that affect their quality of life and severely disrupt family well-being. Fatty acid supplements are natural products with anti-inflammatory properties often used for treatment of ASD symptoms, but their efficacy remains unproven. The objective of the proposed protocol is to quantify the impact of Omega 3-6 on pre-specified biological signatures. The hypotheses were formulated based on data from the investigators previous studies and other published data which suggest that the inflammatory markers, IL-1β, IL-2, and IFNγ are consistently elevated in children with ASD and decreases in these markers correlate with ASD symptom improvement. The investigators long-term goal is to identify effective treatments for ASD.
Interventions
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
DIETARY_SUPPLEMENTCanola Oil Placebo
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
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Sarah Keim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple
Eligibility
Sex/Gender
ALL
Age
2 Years to 6 Years
Healthy volunteers
No
Inclusion criteria
* Age 2-6 years old * ASD diagnosis at Nationwide Children's Hospital within the prior 6 months * ADOS-2 score in autism (severe) range * 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, Angleman Syndromes, Tuberous Schlerosis * Feeding problems precluding consumption of the supplement * Ingredient allergy (canola, fish, or borage seed) * Planned surgeries scheduled within the time frame of trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biological Signatures | Baseline to 90 days post-randomization | Changes in the biological signatures (IL-1β, IL-2, IFNγ) from baseline to the end of the trial. |
| Bioavailability | Baseline to 90 days post-randomization | Group differences in bioavailability; each fatty acid as a percent of total erythrocyte fatty acids at the end of the trial |
| Safety (Adverse Events) | Baseline to 90 days post-randomization | Average number of adverse events per treatment group |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LCPUFA Oil Supplement, Low Dose 25 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days
LCPUFA Oil Supplement: 25 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days | 12 |
| LCPUFA Oil Supplement, Medium Dose 50 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days
LCPUFA Oil Supplement: 50 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days | 12 |
| LCPUFA Oil Supplement, High Dose 75 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days
LCPUFA Oil Supplement: 75 mg/kg of GLA+EPA+DHA as Omega 3-6 oil to be administered twice per day by mouth for 90 days | 13 |
| Canola Oil Equal volume of placebo (canola) oil to be administered twice per day by mouth for 90 days
Canola Oil Placebo: Equal volume of placebo (canola) oil to be administered twice per day by mouth for 90 days | 33 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Excluded due to ineligibility after randomization | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 1 | 2 |
Baseline characteristics
| Characteristic | LCPUFA Oil Supplement, Low Dose | LCPUFA Oil Supplement, Medium Dose | LCPUFA Oil Supplement, High Dose | Canola Oil | Total |
|---|---|---|---|---|---|
| Age, Customized 2-3 years | 7 Participants | 7 Participants | 7 Participants | 15 Participants | 36 Participants |
| Age, Customized 4-6 years | 5 Participants | 5 Participants | 6 Participants | 18 Participants | 34 Participants |
| Baseline Pre-Specified Biological Signatures (cytokines) IFNγ | 8.95 pg/ml STANDARD_DEVIATION 6.4 | 11.22 pg/ml STANDARD_DEVIATION 10.18 | 9.80 pg/ml STANDARD_DEVIATION 7.35 | 16.72 pg/ml STANDARD_DEVIATION 43.17 | 11.67 pg/ml STANDARD_DEVIATION 3.49 |
| Baseline Pre-Specified Biological Signatures (cytokines) IL-1β | 0.10 pg/ml STANDARD_DEVIATION 0.05 | 0.16 pg/ml STANDARD_DEVIATION 0.25 | 0.07 pg/ml STANDARD_DEVIATION 0.05 | 0.10 pg/ml STANDARD_DEVIATION 0.06 | 0.11 pg/ml STANDARD_DEVIATION 0.04 |
| Baseline Pre-Specified Biological Signatures (cytokines) IL-2 | 0.31 pg/ml STANDARD_DEVIATION 0.12 | 0.55 pg/ml STANDARD_DEVIATION 0.96 | 0.23 pg/ml STANDARD_DEVIATION 0.1 | 0.48 pg/ml STANDARD_DEVIATION 0.47 | 0.39 pg/ml STANDARD_DEVIATION 0.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 9 Participants | 13 Participants | 31 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African-American | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 13 Participants |
| Race/Ethnicity, Customized Race Missing | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other or Multiple Races | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Race White | 6 Participants | 6 Participants | 8 Participants | 27 Participants | 47 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 10 Participants | 28 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 33 |
| other Total, other adverse events | 12 / 12 | 11 / 12 | 13 / 13 | 31 / 33 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 33 |
Outcome results
Primary
Bioavailability
Group differences in bioavailability; each fatty acid as a percent of total erythrocyte fatty acids at the end of the trial
Time frame: Baseline to 90 days post-randomization
Population: 11 participants were not included in analysis due to missing a scheduled blood draw at 90 days post randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCPUFA Oil Supplement, Low Dose | Bioavailability | EPA | 1.95 mol% | Standard Deviation 1.04 |
| LCPUFA Oil Supplement, Low Dose | Bioavailability | DHA | 4.33 mol% | Standard Deviation 1.26 |
| LCPUFA Oil Supplement, Medium Dose | Bioavailability | DHA | 3.61 mol% | Standard Deviation 1.39 |
| LCPUFA Oil Supplement, Medium Dose | Bioavailability | EPA | 1.80 mol% | Standard Deviation 1.56 |
| LCPUFA Oil Supplement, High Dose | Bioavailability | EPA | 3.00 mol% | Standard Deviation 2.45 |
| LCPUFA Oil Supplement, High Dose | Bioavailability | DHA | 4.75 mol% | Standard Deviation 1.76 |
| Canola Oil | Bioavailability | EPA | 0.80 mol% | Standard Deviation 0.33 |
| Canola Oil | Bioavailability | DHA | 2.46 mol% | Standard Deviation 0.92 |
Primary
Biological Signatures
Changes in the biological signatures (IL-1β, IL-2, IFNγ) from baseline to the end of the trial.
Time frame: Baseline to 90 days post-randomization
Population: 11 participants were not included in analysis due to missing a scheduled blood draw at 90 days post randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCPUFA Oil Supplement, Low Dose | Biological Signatures | IL-1β | -0.01 pg/ml | Standard Deviation 0.64 |
| LCPUFA Oil Supplement, Low Dose | Biological Signatures | IFNγ | -1.04 pg/ml | Standard Deviation 0.67 |
| LCPUFA Oil Supplement, Low Dose | Biological Signatures | IL-2 | -0.10 pg/ml | Standard Deviation 0.34 |
| LCPUFA Oil Supplement, Medium Dose | Biological Signatures | IL-1β | -0.02 pg/ml | Standard Deviation 0.38 |
| LCPUFA Oil Supplement, Medium Dose | Biological Signatures | IFNγ | -1.43 pg/ml | Standard Deviation 0.56 |
| LCPUFA Oil Supplement, Medium Dose | Biological Signatures | IL-2 | -0.29 pg/ml | Standard Deviation 0.01 |
| LCPUFA Oil Supplement, High Dose | Biological Signatures | IL-2 | -0.11 pg/ml | Standard Deviation 0.26 |
| LCPUFA Oil Supplement, High Dose | Biological Signatures | IL-1β | -0.03 pg/ml | Standard Deviation 0.16 |
| LCPUFA Oil Supplement, High Dose | Biological Signatures | IFNγ | 2.99 pg/ml | Standard Deviation 0.19 |
| Canola Oil | Biological Signatures | IL-1β | 0.11 pg/ml | Standard Deviation 0.09 |
| Canola Oil | Biological Signatures | IFNγ | -9.77 pg/ml | Standard Deviation 43.92 |
| Canola Oil | Biological Signatures | IL-2 | 0.01 pg/ml | Standard Deviation 0.24 |
Primary
Safety (Adverse Events)
Average number of adverse events per treatment group
Time frame: Baseline to 90 days post-randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCPUFA Oil Supplement, Low Dose | Safety (Adverse Events) | 4.5 events per person | Standard Deviation 2.35 |
| LCPUFA Oil Supplement, Medium Dose | Safety (Adverse Events) | 3.33 events per person | Standard Deviation 2.23 |
| LCPUFA Oil Supplement, High Dose | Safety (Adverse Events) | 5.62 events per person | Standard Deviation 2.81 |
| Canola Oil | Safety (Adverse Events) | 3.88 events per person | Standard Deviation 2.53 |