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The Children’s’ Autism Metabolome Project (CAMP): Anatomy of a Clinical Study Employing Metabolomics to Identify Novel Metabolic Subtypes of Autism Spectrum Disorder (ASD)
ASD is a complex spectrum of neurodevelopmental disorders with heterogeneous underlying genetic, metabolic, and environmental causes. The CAMP (ClinicalTrials.gov Identifier NCT02548442) study, the largest clinical study using metabolomics based methodologies, is being conducted to validate biomarkers identified in three previous studies of banked blood samples and to better understand the metabolism of children with ASD. Metabolomic analyses of ASD may be useful in identifying biomarkers that can provide insight into the role that biochemical disorders, the gut microbiome, dietary and environmental factors play in ASD. The metabolic signatures of ASD can be useful in parsing the broad autistic spectrum into more homogeneous and clinically significant subtypes. Better understanding of metabolic subtypes or metabotypes of ASD can lead to early diagnosis, development and selection of more precise therapeutic intervention, as well as better understand of the efficacy of current interventions within metabotypes.
Objectives:
Enroll a total of 1500 subjects comprised of ASD, development delay (DD) and typically developing (TD) children ages 18-48 months. Employ a robust experimental platform based on orthogonal mass spectrometry methodologies comprised of both targeted and non-targeted metabolomics methods. Identify metabolic perturbations associated with ASD specifically focusing on the identification of metabotypes of ASD through measurement of metabolic differences in patients across the spectrum as compared to DD and TD children.
Methods:
The CAMP is being conducted at 8 locations. Diagnosis is based on DSM-V confirmed by Autism Diagnostic Observation Schedule (ADOS) for ASD and the Mullen scales of early learning for DD. Extensive data is being collected regarding medical history, diet, supplements and family history. Blood and urine samples are being collected for metabolomics and gene expression analysis. The numbers of patients for each group (ASD, TD or DD) were determined by a power analysis study, with the goal of providing a maximum power of 0.9 for pairwise comparisons in univariate and multivariate analyses.
Results:
The experimental platform developed for the CAMP study detects 2.2 times more metabolite related features then the previous results generated from the three smaller banked blood studies. The number of subjects allows for detection of novel, less prevalent metabotypes associated with ASD. The CAMP study metabolomics data will be analyzed in conjunction with cohort information, study demographic data, subject metadata, RNA expression and genotype information to better understand the metabolic profiles associated ASD.
Conclusions:
The CAMP study will provide the largest set of samples collected under procedures designed for metabolomics analysis. Metabolomics will provide a valuable additional perspective on this complex disorder. Collection of blood plasma and urine, as well as RNA and DNA, will allow an integrated evaluation of the metabolic phenotype of ASD. Better understanding of the metabolic phenotype of ASD has the potential to enable earlier diagnosis, identification of biochemical alterations in patients across the spectrum that will provide targets for new treatments as well as better understanding about who benefits from current treatments.