Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder
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|ClinicalTrials.gov Identifier: NCT03835117|
Recruitment Status : Recruiting
First Posted : February 8, 2019
Last Update Posted : August 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|Autism Spectrum Disorder||Drug: Wide-spectrum nutritional supplement Other: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Prospective Randomized 12-week Double-Blind Placebo-Controlled Cross-over|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder (ASD)|
|Actual Study Start Date :||February 1, 2020|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||April 2021|
Experimental: Wide-spectrum nutritional supplement
The Wide-spectrum nutritional supplement used will be a combination of NeuroNeeds: SpectrumNeeds and QNeeds. Weight based dosing will be used. The daily serving size will be divided into two oral daily doses in the form of a powder which can be mixed into liquid or food. Together, there are 34 different dietary supplements in the products. Except for ubiquinol, all of these nutrients are provided in a powder form in SpectrumNeeds. Ubiquinol is provided separately in QNeeds gel capsules. These capsules can be swallowed whole, or cut with scissors and the contents squeezed out and added to SpectrumNeeds just before ingestion.
Drug: Wide-spectrum nutritional supplement
Comprehensive powder with 33 dietary supplements and 1 dietary supplement via gel capsule.
Other Name: NeuroNeeds: Spectrum Needs, NeuroNeeds:Q Needs
Placebo Comparator: Placebo control
Participants randomized to receive placebo will take placebo in an oral form divided into powder and a gel capsule in the same manner as treatment. For the second phase of the cross over, participants will be part of the opposite group they were assigned to in Phase I (Placebo or Treatment). Quantities for placebo or treatment will match across phases for each subject, utilizing the same weight based dosing.
Inactive placebo comparator
- Change in mitochondrial activity in study patients [ Time Frame: Baseline, Week 12, Week 24 ]Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment.
- Change in the Childhood Autism Rating Scale (CARS) score [ Time Frame: Baseline, Week 12, Week 24 ]The Childhood Autism Rating Scale is a 15-item clinician-rated scale that measures the severity of core ASD symptoms of social communication and restricted and repetitive patterns of behavior, interests, or activities. Each item is scored on a 4 point scale of severity from 1 (None/Minimal) to 4 (Severe). The measure is the total score of the 15 items in which a score of 15-27.5 reflects minimal to no severity of symptoms, 28-33.5 reflects mild to moderate severity of symptoms, and a score of 34 or higher reflects severe symptoms.
- Change in the Clinical Global Impression scale (CGI) score [ Time Frame: Baseline, Week 12, Week 24 ]The Clinical Global Impression - Severity scale (CGI-S) is a clinician rated 7-point measure of overall symptomatic severity of psychopathology. Scores range from 1 (Normal, not at all ill) through 4 (Moderately ill) to 7 (Among the most extremely ill patients). The Clinical Global Impression - Improvement scale (CGI-I) is the companion measure that evaluates the change in the patient's symptoms relative to baseline. Scores range from 1 (Very much improved) through 4 (No Change) to 7 (Very much worse). Ratings are reflected in a single total score, in which a score of 2 (Much Improved) or 1 (Very Much Improved) on the CGI-I will be used as a secondary measure to define positive response.
- Change in the Children's Yale-Brown Obsessive Compulsive Scale modified for Autism Spectrum Disorder (CYBOCS-ASD) score [ Time Frame: Baseline, Week 12, Week 24 ]The Children's Yale-Brown Obsessive Compulsive Scale modified for Autism Spectrum Disorder is a 5-item clinician-rated measure to evaluate severity of repetitive behavior in children with ASD. Each item is scored on a 5 point scale from 0 (None) to 4 (Extreme) for the severity of: Time Spent, Interference in everyday life, Distress, Resistance, and Degree of Control over the behavior. A decrease in the total score of the 5 items, ranging from 0 to 20, will be used as a secondary measure to define positive response.
- Change in the Aberrant Behavior Checklist (ABC) scores [ Time Frame: Screening, Week 12, Week 24 ]The Aberrant Behavior Checklist is a 58-item caregiver questionnaire consisting of five subscales: hyperactivity, irritability, social withdrawal, stereotypic behavior and inappropriate speech in children with developmental disabilities. A higher score indicates more frequent aberrant behaviors. Our secondary measures are the subscale scores for Irritability (15 item), Social Withdrawal (16 item) and Hyperactivity (16 item). Each item rates behavior severity on a 4 point scale from 0 (Not at all a problem) to 3 (The problem is severe in degree). A decrease in the subscale scores, ranging from 0 to 45 (Irritability), 48 (Social Withdrawal) and 48 (Hyperactivity), will be used as secondary measures to define positive response.
- Change in the Parent-rated Anxiety Scale for ASD (PRAS-ASD) score [ Time Frame: Baseline, Week 12, Week 24 ]The Parent-rated Anxiety Scale for Autism Spectrum Disorder is a 25-item scale that measures anxiety in youth with ASD. Each item rates the severity of a behavior on a 4 point scale from 0 (None/not present) to 3 (Severe/Very frequent and a major problem). A decrease in the total score of the 25 items, ranging from 0 to 75, will be used as a secondary measure to define positive response to intervention.
- Change in the Caregiver Strain Questionnaire (CGSQ) score [ Time Frame: Baseline, Week 12, Week 24 ]The Caregiver Strain short-form questionnaire is a 7-item measure of self-reported strain experienced by caregivers of children with behavioral disorders. Each item rates the severity of interference in the quality of the caregiver's life on a 5 point scale from 0 (Not at All) to 4 (Very Much). A decrease in the total score of the 7 items, ranging from 0 to 28, will be used as a secondary measure to define positive response.
- Change in the Vineland III Caregiver score [ Time Frame: Baseline, Week 12, Week 24 ]The Vineland III Caregiver is a 381-item parent-reported measure of adaptive behavior in children with developmental and intellectual disabilities. The Vineland is comprised of three sub scores for the following domains: Communication, Daily Living Skills, and Socialization. The frequency of adaptive behaviors for each item is scored on a scale from 0 (Never) to 2 (Usually). The total adaptive score is reflected as a composite score of the sub domains (which is determined by age norms) in which a higher total score reflects higher functioning. An increase in the total score or sub domain scores will be used as a secondary measure to define positive response to intervention.
- Evaluate intervention safety [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 ]Columbia-Suicide Severity Rating Scale: a suicide risk assessment that identifies presence and severity of suicidal ideation, planning, and behavior, as well as non-suicidal self-harm behaviors. Presence of any of these behaviors during the course of study enrollment will be considered an adverse event.
- Evaluate intervention safety [ Time Frame: Screening, Week 12, Week 24 ]Routine complete blood counts will be collected to determine whether treatment-emergent basic blood chemistry is altered. Presence of any changes during the course of study enrollment will be evaluated by the treating physician and determined clinically significant or not clinically significant. If determined by the treating physician, a change will be considered an adverse event.
- Evaluate intervention safety [ Time Frame: Screening, Week 12, Week 24 ]Routine comprehensive blood panels will be collected to determine whether treatment-emergent basic blood chemistry is altered. Presence of any changes during the course of study enrollment will be evaluated by the treating physician and determined clinically significant or not clinically significant. If determined by the treating physician, a change will be considered an adverse event.
- Evaluate intervention effect on cellular regulatory pathways known to be implicated in ASD [ Time Frame: Screening, Week 12, Week 24 ]Evaluation of a variety of research biomarkers, including peripheral blood mononuclear cell, plasma, DNA, red blood cells, and oxidative stress rates. Treatment-emergent change in these biomarkers will indicate that a change has occurred at the cellular level.
- Examine the change in attention to social stimuli [ Time Frame: Baseline, Week 12, Week 24 ]Participants will watch a video with social and non-social stimuli. Eye movements and visual fixation will be measured with eye tracking software. Change in percentage of time spent looking at social stimuli will be measured.
- Examine the change in cognitive ability [ Time Frame: Screening, Week 12, Week 24 ]Differential Abilities Scale-II: cognitive abilities across core domains: verbal, nonverbal, spatial. Subtests: Verbal comprehension: 42-item domain, raw score 0-23. Naming vocabulary: 34-item domain, raw score 0-28. Word definitions: 35-item domain, raw score 0-25. Verbal similarities: 33-item domain, raw score 0-28. Picture similarities: 32-item domain, raw score 0-23. Picture similarities: 50-item domain, raw score 0-34. Matrices: 56-item domain, raw score 0-33. Pattern construction: 35-item domain, raw score 0-74. Copying: 20-item domain, raw score 0-36. Recall of designs: 22-item domain, raw score 0-43. All subdomains have a t-score range of 10-90. Verbal ability standard score ranges from 30-170. Nonverbal ability standard score ranges from 32-170. Spatial ability standard score ranges from 34-170. Total General Conceptual Ability standard score ranges from 30-170. Subtests and item sets given vary by participant age
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03835117
|Contact: Richard E Frye, MD, PhDfirstname.lastname@example.org|
|Contact: Amanda Jensen, BSemail@example.com|
|United States, Arizona|
|Phoenix Children's Hospital||Recruiting|
|Phoenix, Arizona, United States, 85016|
|Contact: Richard E Frye, MD, PhD 602-933-0681 firstname.lastname@example.org|
|Principal Investigator: Richard E Frye, MD, PhD|
|Sub-Investigator: Richard Boles, MD|
|Principal Investigator:||Richard E Frye, MD, PhD||Phoenix Children's Hospital|