Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder often with
life-long consequences that affects young children during critical developmental periods. The
Centers for Disease Control estimates that ASD affects as many as 17 per 1000 children (1 in
59) in the United States suggesting that the prevalence is higher than previous
estimates.Despite the dramatic rise in the detected prevalence of ASD over the past two
decades, there is no effective medical treatment for core ASD symptoms (social communication
and repetitive behavior), the closely associated problem of language impairment, or the
underlying pathophysiology of ASD. Currently, the only accepted treatment for core ASD
symptoms is behavior therapy, which may entail intensive one-on-one treatment over several
years.

The primary aims of this study are to evaluate the effect of a wide-spectrum nutritional
supplement on mitochondrial function in individuals with ASD. Participants entered into the
trial will have abnormalities in mitochondrial function that are known to be associated with
ASD (approximately 50+% of children with ASD) but are not diagnostic of mitochondrial
disease. The investigators hypothesize that nutritional supplements designed for children
with ASD have a physiological action of normalizing mitochondrial function and cellular
physiology throughout the body.

To test whether the targeted nutritional supplement is superior to placebo, the investigators
will study 50 children, between the ages of 4 years to 14 years, with confirmed ASD and known
abnormal variations in mitochondrial at baseline. Participants will be randomly assigned to
receive active treatment or placebo for 12-weeks under double-blind conditions and at the end
of the 12 weeks switch to the opposite condition after a 2-week wash out period.
Mitochondrial function will be measured at baseline and after each treatment arm in order to
determine if the supplement positively influences cellular biochemistry. The investigator
will also evaluate the effectiveness of the supplement on core and associated ASD symptoms
using several behaviors assessments.

Inclusion Criteria:

- Weight ≥ 15 kg and ≤ 100kg;

- DSM-5 diagnosis of Autism Spectrum Disorder as established by formal clinical
assessment which includes a gold-standard tool such as the Autism Diagnostic
Observational Schedule.

- Current Clinical Global Impression Severity score ≥ 4 on ASD

- IQ at least 40 as measured by the Leiter-R

- Stable educational and therapy plan (one month) with no planned changes in the
intensity of treatment for 12 weeks.

- English is spoken in the home and at least one parent is able to read, write and speak
English.

- Stable medication (no changes in past 6 weeks and no planned changes for the study
duration.

- Electron Transport Chain Complex (I, II, III, IV) or Citrate Synthase Activity which
is >= 2.0 Standard Deviation Above or Below Average (outside the normal range)

Exclusion Criteria:

- IQ below 40 as measured by the Leiter-R

- Presence of serious behavioral problems (tantrums, aggression, self-injury) for which
another treatment is warranted.

- Significant medical condition by history or by physical examination or lab tests that
would be incompatible with the treatment.

- Children taking anticonvulsant medication for seizures or active epilepsy.

- Diagnosis of Mitochondrial Disease