Transgenerational Metabolic-Immune Biomarkers of Neurological and Neurodevelopmental Disorders

Researchers in the Neurodevelopmental Division at Phoenix Children's Hospital are conducting a study about mitochondrial function in children with autism spectrum disorder (ASD). The study involves up to 5 visits to Phoenix Children's Hospital with fasting blood draws, behavioral assessments, and/or questionnaires. Other samples may be collected when appropriate.

This study is currently recruiting.

There is no cost for visits or study-related exams.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Mitochondrial Diseases; Brain Tumor; Autism Spectrum Disorder; Psychiatric Disorder; Mitochondrial Pathology

Detailed Description

Mitochondria are essential for a wide range of functions in almost every cell in our body. Best known for their role in adenosine triphosphate (ATP) production, mitochondria are also closely involved in a wide variety of cell functions such as calcium buffering, redox regulation, apoptosis and inflammation, and regulate metabolism through several mechanisms, including epigenetic changes. ATP produced is essential for many cellular systems. Thus, abnormal mitochondrial function can adversely affect cellular systems by several mechanisms.

Given the important role of the mitochondria in cellular function, individuals with classic mitochondrial disease demonstrate devastating symptoms, particularly in tissues that have high-energy demands such as the brain, muscles, gastrointestinal (GI) tract and immune system. Mitochondrial dysfunction contributes to the pathophysiology of more common diseases, including psychiatric diseases, neurodegenerative disorders, neurological disorders including migraine and seizures, persistent systemic inflammation, cardiac disease, cancer and diabetes. Mitochondrial dysfunction also effects a significant portion of individuals with autism spectrum disorder (ASD) as well as genetic syndromes associated with ASD.

One of our goals is to develop a method using the Seahorse Analyzer to measure individual variations in mitochondrial function which can identify children with medical disorders and mitochondrial dysfunction without an invasive muscle biopsy. In order to establish comprehensive profiles of mitochondrial function for individuals with known neurological and neurodevelopmental disorders, we will compare blood, urine, and stool from these individuals to those of healthy, typically developing (TD) children. The relationship between mitochondrial function, development, and behavior will be assessed by performing standard developmental testing. In addition, in patients who have a procedure that produces leftover tissue, we will examine the mitochondrial function in that tissue and correlate it with findings from blood.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Richard E Frye, MD, PhD; Phone Number: (602) 933-0681; Email: rfrye@phoenixchildrens.com
• Study Contact Backup: Name: Sarah Vassall, BS, BA; Phone Number: (602) 933-0853; Email: svassall@phoenixchildrens.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Southwestern Research and Resource Center
      • Contact: Sophia Crisler; Phone Number: (480) 582-9467
      • Contact: Christopher J Smith, PhD; Phone Number: 602-218-8192
      • Principal Investigator: Richard Frye, MD, PhD
  • New York
    • Brooklyn, New York, United States, 11203
      • State University of New York, Downstate
      • Contact: Daniel Mishan; Phone Number: (718) 270-2272; Email: autism.research@downstate.edu
      • Contact: Harris Huberman, MD; Phone Number: 718-270-2272; Email: harris.huberman@downstate.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

400 children aged 0 years to 17 years 11 months with a neurological, psychiatric or neurodevelopmental disorder.

250 children in this sample will have a known diagnosis of ASD: 50 children with a diagnosed MD (ASD/MD), 50 children with ruled out MD (ASD/NoMD), 150 children with ASD and unknown MD status.

Comparison groups: 50 children with epilepsy (without ASD), 50 with psychiatric disorders, 50 with brain tumors (without ASD) 50 with a diagnosed MD (without ASD)

Control group: 100 TD children (50 siblings of children with ASD and 50 without any siblings with ASD or developmental delay).

Description

Inclusion Criteria (ASD):

1. ASD, as defined by either a gold standard measure for ASD diagnosis, the Autism Diagnostic Observation Schedule (ADOS); the Autism Diagnostic Interview-Revised (ADI-R); and/or a comprehensive assessment that is consistent with ASD, in the opinion of the principal investigator. For those the PI believes a prospective diagnosis of ASD is warranted, a formal diagnostic assessment will be scheduled at screening.
2. 0 years through 17 years 11 months of age

Inclusion Criteria (TD, MD, Epilepsy, Brain Tumor, Psychiatric)

1. 0 years to 17 years 11 months of age

Exclusion Criteria (All):

1. History of a significant adverse reaction to a prior blood draw
2. In females of reproductive age, pregnancy or plans to become pregnant
3. Any other historical event/information that may, in the opinion of the PI, be a reason to exclude the child from participation.

Study Plan

How is the study designed?

Number of groups / cohorts

9

Cohorts and Interventions

Group / Cohort
ASD (General); 150 children with ASD and unknown MD status
ASD (With MD); 50 children with ASD and confirmed MD
ASD (No MD); 50 children with ASD and ruled out MD
Epilepsy; 50 children with epilepsy (primary) and no ASD
Brain Tumor; 50 children with brain tumor (primary) and no ASD
Psychiatric Disorder; 50 children with psychiatric disorder (primary) and no ASD, using lithium treatments
MD (No ASD); 50 children with MD (primary) and no ASD
TD (With ASD Sibling); 50 TD children with a sibling with ASD/neurodevelopmental delay
TD (No ASD Sibling); 50 TD children with no siblings with ASD/neurodevelopmental delay

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mitochondrial Reserve Capacity measured using the Seahorse XR Flux Analyzer	Children with ASD will be differentiated from all other cohorts and have a specific pattern of mitochondrial dysfunction that will be different from and comparable to other groups of children in the study (e.g. mitochondrial disease without autism, typically developing, autism with mitochondrial disease, and developmental delay). It is hypothesized that these children will have a more pronounced delay in their development and will have a higher probability for poor developmental and behavioral outcomes. This will be evaluated using a Seahorse XR flux analyzer to generate a maximal reserve capacity value.	Up to one year

Collaborators and Investigators

• Sponsor: Southwest Autism Research & Resource Center
• Collaborators: State University of New York - Downstate Medical Center
• Investigators: Principal Investigator: Richard E Frye, MD, PhD, Phoenix Children's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Metabolic Diseases; Child Development Disorders, Pervasive; Mitochondrial Diseases; Problem Behavior; Mental Disorders; Autism Spectrum Disorder; Neurodevelopmental Disorders
• Other Study ID Numbers: Mito Tissue

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The PI may collaborate with other researchers to perform analyses on individual samples that have been stored for future research. In this case, the coded data with characteristics about the participant will be shared as appropriate (e.g., diagnostic status).
• IPD Sharing Time Frame: After completion of initial study
• IPD Sharing Access Criteria: Researchers must have an established protocol with relevant interest to the samples and data stored.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No