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Mitochondrial Disease and Dysfunction in Neurological and Neurodevelopmental Disorders

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ClinicalTrials.gov Identifier: NCT04322734
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : March 26, 2020
Sponsor:
Information provided by (Responsible Party):
Phoenix Children's Hospital

Tracking Information
First Submitted Date March 24, 2020
First Posted Date March 26, 2020
Last Update Posted Date March 26, 2020
Actual Study Start Date January 1, 2020
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 24, 2020)
Mitochondrial Reserve Capacity measured using the Seahorse XR Flux Analyzer [ Time Frame: Up to one year ]
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.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Mitochondrial Disease and Dysfunction in Neurological and Neurodevelopmental Disorders
Official Title Mitochondrial Disease and Dysfunction in Neurological and Neurodevelopmental Disorders
Brief Summary

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.

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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
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. Such tissues include but are not limited to cerebrospinal fluid (CSF), muscle, or GI tissue. We will examine all collected tissues for biomarkers of mitochondrial dysfunction, as well as evaluate single nucleotide polymorphisms (SNPs) and peripheral blood mononuclear cells (PBMCs) in patients and biological parents as reliable risk factors for developing mitochondrial dysfunction. Parent biological information may be acquired through blood and saliva samples. Baby teeth, medical history and resident location will be analyzed to assess environmental exposures.
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).

Condition
  • Autism Spectrum Disorder
  • Mitochondrial Pathology
  • Epilepsy
  • Brain Tumor
  • Psychiatric Disorder
  • Mitochondrial Diseases
Intervention Not Provided
Study Groups/Cohorts
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 24, 2020)
500
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 1, 2025
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria

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.
Sex/Gender
Sexes Eligible for Study: All
Ages up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Richard E Frye, MD, PhD (602) 933-0681 rfrye@phoenixchildrens.com
Contact: Sarah Vassall, BS, BA (602) 933-0853 svassall@phoenixchildrens.com
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04322734
Other Study ID Numbers Mito Tissue
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Yes
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).
Time Frame: After completion of initial study
Access Criteria: Researchers must have an established protocol with relevant interest to the samples and data stored.
Responsible Party Phoenix Children's Hospital
Study Sponsor Phoenix Children's Hospital
Collaborators Not Provided
Investigators
Principal Investigator: Richard E Frye, MD, PhD Phoenix Children's Hospital
PRS Account Phoenix Children's Hospital
Verification Date March 2020