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Clinical and Immunological Investigations of Subtypes of Autism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00298246
Recruitment Status : Completed
First Posted : March 1, 2006
Last Update Posted : October 6, 2017
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

The purpose of this study is to learn more about autism and its subtypes. Autism is a developmental disorder in which children have problems with communication and social skills and display restricted interests and repetitive behaviors.

This study has several goals. One aim is to look at types of autism that are known, such as the regressive subtype, (where skills are lost). We will explore whether there is a unique change in immune functioning related to this subtype. Another aim is to serve as one of the sites that will pilot a larger natural history study, entitled Autism Phenome Project. The goal is to further understand autism by identifying other subtypes.

We will look at several types of medical issues that may be related to autism, including immunologic problems. Children will be followed over the course of several years. We aim to capture medical problems that may be related to autism as they develop, and study outcomes in areas such as behavior and language, in order to explore known and new subtypes of autism.

Normally developing children (aged 1) with autism (age 1, and developmental delays other than autism (age 1), may be eligible for this study.

Depending on each child's study group and age, participants may undergo the following tests and procedures:

Baseline Visit

  • Medical and developmental history, physical examination, psychological, cognitive and medical tests to assess symptoms of autism or other developmental disorders, photographs of the child's face, collection of hair, urine and baby teeth samples. If available, hair samples from the baby's first haircut and from the biological mother's hair are also collected.
  • Overnight electroencephalogram (EEG): A special cap with electrodes is placed on the child's head to measure brain waves (brain electrical activity) while the child sleeps in the hospital overnight. Healthy volunteers do not undergo this procedure.
  • Magnetic resonance imaging (MRI) scan: The child stays in the scanner, lying still for 10 to 15 minutes at a time. Since it may be difficult for the child to lie still, the test may be scheduled for a time when the child is likely to be sleepy, or the child may be sedated.
  • Lumbar puncture (for children in the autism). This test and the MRI may be done under sedation.

Follow-Up Visits

Follow-up visits are scheduled at different intervals, depending on study group, age and aspect of the study the child is enrolled in. The visits include a short interview session with the child's caregiver and assessment of the child's development and behavior. Some of the assessment measures used during the baseline examination are repeated, including symptoms ratings, behavioral tests and a blood test. For some children, the final visit will include repeats of the medical procedures.

Condition or disease
Autism Spectrum Disorders Seizures

Detailed Description:


The current investigation focuses on finding meaningful subtypes of autism. Our objectives include using comprehensive and longitudinal medical assessments and behavioral testing to find subgroups of children with autism with profiles that comprise distinct biological/behavioral phenotypes.

Specific goals include determining if there is a unique alteration in immune function among autistic children with a regressive clinical course, and identifying autism-specific sleep and electroenchelalogram (EEG) abnormalities, and other potential biomarkers.

Study Population:

We are conducting a longitudinal natural history study of 140 children with autism, 12 to 84 months of age at study entry. We also are following as many as 75 typically developing children, and 50 children with Developmental Delay to serve as age-/sex-matched controls.


Systematic prospective evaluations are being utilized to determine diagnostic and functional outcomes, and evaluate behavioral, medical and immunologic functioning. These evaluations include comprehensive medical history, behavioral assessment, physical and neurologic examination, polysomnography (PSG) and EEG, and blood work for laboratory assays. Baseline evaluations also included MRI and lumbar puncture (the latter was only subjects with autism). In any investigation of behavioral outcomes and potential biomarkers, repeated assessments are necessary to determine whether findings are due to state versus trait alterations. Thus, key elements of the assessments are repeated every 6 to 12 months, depending on the child s age.

Outcome Variables:

Measures of autism symptoms and severity, along with cognitive and adaptive behavior profiles, will be used as behavioral outcome variables.

Results of physical and neurological examinations, genetic testing, EEGs, polysomnograms, MRI scans and laboratory assays of blood and CSF will be tested for their utility as biomarkers of autism s core symptoms or identification of etiologically related subgroups of patients.

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Study Type : Observational
Actual Enrollment : 557 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical and Immunological Investigations of Subtypes of Autism
Study Start Date : February 22, 2006
Study Completion Date : March 15, 2017

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Behavioral profiles [ Time Frame: 6 to 12 months ]
  2. Immune markers [ Time Frame: 6 to 12 months ]
  3. Sleep/EEG findings [ Time Frame: 6 to 12 months ]
  4. Neuroimaging findings [ Time Frame: 6 to 12 months ]
  5. Other laboratory findings [ Time Frame: 6 to 12 months ]
  6. Genetic abnormalities [ Time Frame: 6 to 12 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Year to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • There are 3 participant groups in this study.

    • AUT: Children with autism (diagnosed with autistic disorder according to DSM-IV criteria). This group will include children that may be dichotomized as with regression and without regression.
    • DD: Children with nonspectrum developmental delays
    • TYP: Children deemed to be typically developing
    • Accrual numbers are to include 140 children in the AUT group, 50 children in the DD group and 75 children in the TYP group.
  • AUT: Children are included if they meet DSM-IV criteria for autistic disorder, based on ADI-R and ADOS and clinical judgment. Those meeting research criteria for autism will be included.
  • Regression is defined as: Language loss: Loss of at least 3 spontaneously meaningful words (excluding mama or dada) used for at least a month, and lost for at least a month.AND/OR Nonverbal communication/social loss: Loss of more than one nonverbal communicative behavior (e.g. gestures, joint attention, eye contact, imagination, pretend play, sharing, showing, watching children, orienting to name, social smiling, social games, spontaneous imitation of actions, response to social overtures). Although there is overlap in the age period for regression specified in this protocol (regression between 15-30 months) and that described for childhood disintegrative disorder (CDD) (the DSM-IV criteria for indicate apparently normal development for the first 2 years after birth ), the criteria for CDD also indicate a diagnosis can only be made if symptoms are not better accounted for by another pervasive developmental disorder such as autism. Symptoms of CDD that separate it from autism include loss of acquired skills in areas such as motor skills and bowel or bladder control, while the focus of the current study is on regression in core symptoms of autism (i.e. socio-communicative skills). Thus, the currently protocol will include children with regression over 2 who meet criteria for autism, but not those who only meet criteria for CDD.
  • DD: Developmental scores (Performance Quotient and Verbal Quotient) greater than 1.5 standard deviations below mean on Mullen Scales of Early Learning
  • TYP: No diagnosis of developmental delay, and no first-degree relatives with a history of autism spectrum disorders.


  • Diagnosis of cerebral palsy. For the typical controls only, a history of extremely low birth weight (due to prematurity or intrauterine growth failure).
  • If behavioral management issues (e.g. self-injury, aggressiveness) are severe to the extent that the screening protocol was aborted.

Information from the National Library of Medicine

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): NCT00298246

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
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Principal Investigator: Susan E Swedo, M.D. National Institute of Mental Health (NIMH)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00298246    
Other Study ID Numbers: 060102
First Posted: March 1, 2006    Key Record Dates
Last Update Posted: October 6, 2017
Last Verified: March 15, 2017
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Neurodevelopmental Disorders
Neurological Disorder
Children- Onset
Pervasive Developmental Disorder
Healthy Volunteer
Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Neurologic Manifestations
Nervous System Diseases