Clinical trial NCT02548442: Children's Autism Metabolome Project
Official title: Children's Autism Metabolome Project (CAMP): Development and Clinical Evaluation of the Stemina Metabolic Biomarker-Based Test to Diagnose Autism Spectrum Disorder in Early Childhood
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Autism Spectrum Disorder
Developmental Disorder
Lead sponsor: Stemina Biomarker Discovery, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Mental Health (NIMH)
name: Nancy Lurie Marks Family Foundation
First posted: 2015-09-14
Enrollment: 1102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be identified as autism spectrum disorder (ASD) or developmentally delayed (DD) subjects by standard behavioral techniques; Typically developing (TD) subjects will be recruited from the communities in which the autism research centers are situated. The ADOS-2 (research reliable), the Mullen Scales of Early Learning (MSEL), as well as an evaluation based on the DSM-V checklist will be administered to each subject enrolled in the study suspected to have a developmental delay or autism. Typically developing children enrolled in the study will be given an MSEL and a Social Communications Questionnaire (SCQ) evaluation to document that they are neither ASD nor DD subjects.

Brief summary: Development and Clinical Evaluation of the Stemina Metabolic Biomarker-Based Test to Diagnose Autism Spectrum Disorder in Early Childhood.

Detailed description: The purpose of this study is to identify metabolitic signatures in blood plasma and/or urine using a panel of biomarker metabolites that differentiate children with autism spectrum disorder (ASD) from children with delayed development (DD) and/or typical development (TD), to develop an algorithm that maximizes sensitivity and specificity of the biomarker profile, and to evaluate the overall algorithm as a diagnostic tool.

A secondary objective is to define metabolites capable of classifying subtypes of ASD that may increase understanding of the metabolic basis of the condition, as well as inform on personalized therapy.

The population targeted for this study includes children aged 18 months to 48 months, diagnosed with ASD or DD using behavioral criteria, and TD children, identified as having no indications of ASD or DD using behavioral criteria. The original target size for the study was 1500 subjects divided equally between the three groups. The targeted male:female ratio is 4:1 in all three groups. During the study, it was determined that biomarkers capable of identifying ASD subjects could be obtained using a total of 1100 subjects divided with 58% ASD, 25%TD, and 17% DD. If the diagnostic biomarkers identified in the study do not perform well in females during the biomarker discovery phase, the study may be expanded to recruit more females to examine the possibility of a female-specific diagnostic test.

Subjects will be qualified for entry into the study and will be invited to participate. On the first study day, subjects' parents will sign an informed consent form and will be asked questions on the mother's pregnancy and of both parents' medical history. A complete medical history, a physical examination, and information needed to obtain a diagnosis of ASD, DD, or TD will be obtained on the study subject. If possible, a urine sample will be collected during the visit. Up to four tubes of blood (\<25 mLs total) will be drawn at the clinic during the visit or within 14 days following this initial visit. An overnight fast is required prior to the visit where blood will be taken from the subject. A subset of the subjects will be asked to return to the clinic 30-60 days later to obtain a replicate metabolic profile.

The study will be divided into a biomarker discovery/method development phase followed by a validation phase of the analytical methods and algorithm that will be used in the clinical test.

The subjects will be randomized and divided equally between a discovery/training set and a validation set. The training set will be used for discovery of the biomarkers and development of the analytical methods intended for the diagnostic test. The validation sample set will be used to evaluate performance of the final clinical methods and algorithms.

Consent will also be sought from all subjects for follow-up contact up to 5 years following enrollment of the last subject enrolled to determine the accuracy of the original behavioral diagnosis over time. Subjects chosen for follow-up will be identified based on the strength of the diagnosis from the behavioral scores and physician assessments as well as the biomarker profiles observed in individuals.

Eligibility criteria: Inclusion Criteria:

* Age of greater or equal to 18 months and less than or equal to 48 months
* Fulfills the definition of an autism spectrum disorder, developmentally delayed, or typically developing child in the age range 18-48 months, as determined by a clinician or certified practitioner of the appropriate tests and who is knowledgeable in the field; and
* Has parental (or other legal guardian ) informed consent to participate.

Exclusion Criteria:

* Diagnosis with a chronic condition that could interfere with a diagnosis of ASD or DD, (e.g.: a known history of Fragile X, Rett syndrome, Down syndrome, tuberous sclerosis, trisomy 21, inborn errors of metabolism or other genetic disorder that includes some symptoms of autism)
* Fetal alcohol syndrome, or other serious neurological disorder
* Other serious metabolic disorder, psychiatric disorder, or medical condition involving the liver, kidney, pulmonary, cardiovascular or endocrine systems
* A second child within a family in which a sibling has already been enrolled.
* A child who has previously participated in the CAMP-01 study

Primary outcomes:
measure: Metabolites in plasma indicative of autism spectrum disorder.
timeFrame: Within 60 months of sample collection
Secondary outcomes:
measure: Metabolites in plasma that are specific for subtypes of autism spectrum disorder
timeFrame: Within 60 months of sample collection
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Melmed Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Sacramento
country: United States
facility: UC David MIND Institute
state: California
city: Lexington
country: United States
facility: Lurie Center for Autism
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Stemina Biomarker Discovery
name: Robert E Burrier, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: West PR, Amaral DG, Bais P, Smith AM, Egnash LA, Ross ME, Palmer JA, Fontaine BR, Conard KR, Corbett BA, Cezar GG, Donley EL, Burrier RE. Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children. PLoS One. 2014 Nov 7;9(11):e112445. doi: 10.1371/journal.pone.0112445. eCollection 2014.
citation: Smith AM, King JJ, West PR, Ludwig MA, Donley ELR, Burrier RE, Amaral DG. Amino Acid Dysregulation Metabotypes: Potential Biomarkers for Diagnosis and Individualized Treatment for Subtypes of Autism Spectrum Disorder. Biol Psychiatry. 2019 Feb 15;85(4):345-354. doi: 10.1016/j.biopsych.2018.08.016. Epub 2018 Sep 6.