Clinical trial NCT03835117: Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder
Official title: Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder (ASD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Keywords: Mitochondrial Dysfunction
Lead sponsor: Rossignol Medical Center
Sponsor class: OTHER
Collaborators: name: Southwest Autism Research & Resource Center
First posted: 2019-02-08
Enrollment: 16
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Prospective Randomized 12-week Double-Blind Placebo-Controlled Cross-over
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the metabolic effects of a comprehensive wide-spectrum supplement for children with ASD to determine whether it physiologically targets mitochondrial pathways known to be abnormal in children with ASD.The intervention is a commonly used wide-spectrum nutritional supplement, which is theoretically designed to normalize mitochondrial function. The investigators aim to determine if the supplement does have the hypothesized effect on physiology in individuals with ASD. The investigator will enroll up to 50 children, aged 4 to 14 years of age with confirmed ASD and mitochondrial dysfunction, and participation will last 26 weeks.

Detailed description: 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.

Eligibility criteria: 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
* 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:

* Presence of serious behavioral problems (tantrums, aggression, self-injury) for which another treatment is warranted.
* Current Clinical Global Impression Severity score \< 7 (Extremely Ill)
* 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

Primary outcomes:
measure: Change in Mitochondrial Activity in Study Patients: Citrate Synthase
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in Mitochondrial Activity in Study Patients: Complex I
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in Mitochondrial Activity in Study Patients: Complex II
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in Mitochondrial Activity in Study Patients: Complex IV
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
Secondary outcomes:
measure: Change in the Childhood Autism Rating Scale (CARS) Score
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in the Clinical Global Impression Scale (CGI) Score
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in the Children's Yale-Brown Obsessive Compulsive Scale Modified for Autism Spectrum Disorder (CYBOCS-ASD) Score
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in the Aberrant Behavior Checklist (ABC) Scores
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in the Parent-rated Anxiety Scale for ASD (PRAS-ASD) Score
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in the Caregiver Strain Questionnaire (CGSQ) Score
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Change in the Vineland III Caregiver Score
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
measure: Evaluate Intervention Safety
timeFrame: Screening, Baseline, After Week 4, After Week 8, After Week 12, Atter Week 16, After Week 20, After Week 24
measure: Examine the Change in Cognitive Ability
timeFrame: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwestern Research & Resource Center
state: Arizona
Study officials:
affiliation: Rossignol Medical Center, Phoenix AZ
name: Richard E Frye, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Delhey LM, Nur Kilinc E, Yin L, Slattery JC, Tippett ML, Rose S, Bennuri SC, Kahler SG, Damle S, Legido A, Goldenthal MJ, Frye RE. The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. J Clin Med. 2017 Feb 13;6(2):18. doi: 10.3390/jcm6020018.
citation: Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x.
citation: Frye RE, Rossignol DA. Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatr. 2014 Jun 27;2:66. doi: 10.3389/fped.2014.00066. eCollection 2014.