A Study of the Association Between Autism and Immune Changes in the Brain

NCT01322555 | Terminated

• 2 other identifiers: 11011811-M-0118
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- People with autism and autism spectrum disorders have problems with communication, behavior, and socializing, and many also have intellectual and developmental disabilities. The cause of autism is not known, but previous research has suggested an association between autism and immune changes in the brain. Researchers are interested in using the experimental radioactive drug (11C)PBR28, which attaches to a protein in the brain that is involved in immune changes, in positron emission tomography (PET) scanning of people with and without autism to see if there are greater immune changes in those with autism. Objectives: \- To determine if positron emission tomography scanning can be used to evaluate changes in an immune system protein in the brains of people with autism. Eligibility: \- Individuals between 18 and 45 years of age who have been diagnosed with either autism or autism spectrum disorders, or are healthy volunteers. Design:

• Participants will be screened with a physical examination and psychological examination, medical history, questionnaires about behavior and mood, and blood and urine tests.
• Participants will have two imaging studies of the brain at separate study visits. The first study visit will involve a magnetic resonance imaging (MRI) scan to provide a baseline image of the brain. The second study visit will involve PET scan with the radioactive chemical (11C)PBR28 to study immune system proteins in the brain. The MRI scan will take about 40 minutes, and the PET scan will take about 2 hours.
• Participants will have a final study visit 24 hours after the PET scan to provide a final blood sample for testing.

Conditions

Autism Spectrum Disorders; Brain Disease; Autism; Healthy Volunteers

Keywords

PBR28; Positron Emission Tomography (PET); Propofol; Autism; Immune Response; Autism Spectrum Disorders; ASD; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (2)

• [11C]PBR28 uptake in brain as measured using VT (volume of distribution) and VT/fp (divided by free fraction in plasma.

• Compare VT in autism versus healthy volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must have a diagnosis of autistic disorder (299.0) or Asperger s disorder (299.80), as determined using the Diagnostic and Statistical Manual-IV (DSM-IV) and confirmation with the Autism Diagnostic Interview-Revised (Lord 1997) and/or Autism Diagnostic Observation Scale (ADOS). (A diagnosis of Pervasive Developmental Disorder, or PDD, will not suffice for this protocol).
• Subjects must be adults between 18-45 years old.
• Subjects must be healthy based on history and physical examination.
• Subjects must be "binders" to \[11C\]PBR28 as determined via one of two ways: by prior participation in a PET scan with \[11C\]PBR28 or by in vitro testing of their leukocytes. We found that non-binders have markedly reduced affinity of \[3H\]PBR28 to leukocyte membranes. The in vitro binding has shown no overlapping values between binders (\~90%) and non-binders.
• Subjects must either provide informed consent, or they must assent in combination with informed consent by a legal guardian or durable power of attorney (DPA).
• Subjects must be adults between 18-45 years old.
• Subjects must be healthy based on history and physical examination
• Subjects must be binders to \[11 C\]PBR28 (see point 4 above for details)
• Prior to the PET scan, all healthy subjects must have had within the prior year an MRI scan of the brain to rule out significant structural abnormalities.

You may not qualify if:

• Any history of alcohol or substance dependence, as these conditions may alter uptake of \[11C\]PBR28.
• Any history of alcohol or substance abuse within the past 6 months, as these conditions may alter uptake of \[11C\]PBR28.
• Schizophrenia.
• In addition to the diagnosis of autistic disorder, ASD or Asperger, any other Axis I disorder that requires inpatient hospitalization during this study, or is at the time of enrollment worsening relative to baseline. We will not completely exclude all Axis I disorders, because it is typical for patients with autism /ASD to carry comorbid Axis I disorders, including Generalized Anxiety Disorder (GAD), social phobia, obsessive compulsive disorder (OCD), dysthymia, Major Depressive Disorder.
• Intellectual quotient (IQ) less than 30, as including the lowest functioning patients would make the experiment logistically challenging and would broaden heterogeneity too much.
• Clinically significant laboratory abnormalities as assessed by the PI, medically responsible investigator or consultant.
• Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases, poorly controlled seizure disorder, or serious cardiopulmonary disease.
• Active seizure disorder, as defined as having had a seizure in the past year or being on antiepileptic medications for seizures.
• Positive HIV status.
• Head trauma resulting in a period of unconsciousness lasting longer than 5 minutes.
• Exposure to radiation in the past year (i.e., PET from other research), which when combined with this study would be above the allowable limits.
• Positive urine drug screen at time of enrollment.
• Pregnancy at time of scan (beta HCG will be measured in all female patients within 24 hours before start of scan and must be negative).
• In patients who will get an MRI scan at NIH, metallic foreign bodies that would be affected by the MRI magnet, or a fear of enclosed spaces that would prohibit MRI scanning.
• Allergy to propofol or eggs (since egg products are used to formulate propofol),.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, Charman T. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006 Jul 15;368(9531):210-5. doi: 10.1016/S0140-6736(06)69041-7.

  PMID: 16844490 BACKGROUND

• Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology. 2009 Jan;20(1):84-90. doi: 10.1097/EDE.0b013e3181902d15.

  PMID: 19234401 BACKGROUND

• Becker KG. Autism, asthma, inflammation, and the hygiene hypothesis. Med Hypotheses. 2007;69(4):731-40. doi: 10.1016/j.mehy.2007.02.019. Epub 2007 Apr 6.

  PMID: 17412520 BACKGROUND

• Paul S, Gallagher E, Liow JS, Mabins S, Henry K, Zoghbi SS, Gunn RN, Kreisl WC, Richards EM, Zanotti-Fregonara P, Morse CL, Hong J, Kowalski A, Pike VW, Innis RB, Fujita M. Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.

  PMID: 29749279 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder; Brain Diseases; Autistic Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 23, 2011
• First Posted: March 24, 2011
• Study Start: March 4, 2011
• Study Completion: July 14, 2017
• Last Updated: July 5, 2018

Record last verified: 2017-07-14

Locations

US (1)