Targeting Microglial Activation for Treatment of Autism Spectrum Disorder (ASD): A Proof-of-Concept, Target-Engagement Study
Overview
- Phase
- Phase 1
- Intervention
- Minocycline
- Conditions
- Autism Spectrum Disorder
- Sponsor
- University of California, Los Angeles
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Evaluate differences in CNS microglial activation in adults with ASD versus healthy volunteers via in vivo CNS binding of [11C]-DAA1106
- Status
- Suspended
- Last Updated
- 5 years ago
Overview
Brief Summary
Autism spectrum disorders (ASD) are highly disabling, persistent neurodevelopmental disorders. There are no available treatments for core symptoms of ASD or biologically-based clinical biomarkers. Emerging evidence indicates that levels of brain inflammation are increased in ASD. In particular, recent work implicates hyperactivity of microglial cells, the resident immune cells of the brain. However, the functional consequences of microglial activation remain unknown. This study will measure microglial activation in ASD using positron emission tomography (PET) brain imaging. Adult males with ASD (n=15) and healthy controls (n=15) will be recruited for this study and undergo comprehensive clinical and behavioral baseline assessment. All subjects will then undergo baseline PET imaging using a radiotracer that labels activated microglia. Subjects with ASD will then undergo 12-week open label treatment with minocycline, an FDA-approved antibiotic thought to block microglial activation. PET imaging will be repeated at 12 weeks to confirm target engagement. A subset of control subjects will also undergo repeat PET imaging to determine test-retest reliability. During minocycline treatment, ASD subjects will be evaluated every 2 weeks for safety, clinical impression, behavioral functioning, and measures of cognition. Results will provide important information regarding the relationship between levels of brain inflammation, cognitive and behavioral function in ASD.
Investigators
Michael Gandal, MD, PhD
Principal Investigator
University of California, Los Angeles
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Minocycline
Intervention: Minocycline
Outcomes
Primary Outcomes
Evaluate differences in CNS microglial activation in adults with ASD versus healthy volunteers via in vivo CNS binding of [11C]-DAA1106
Time Frame: Data will be collected at PET scan #1, which will take place during screening (Days -28 to 0) for the study
Evaluate the effect of 12-weeks of minocycline exposure on CNS microglial activation in adults with ASD by measuring change in [11C]-DAA1106 binding pre- and post- treatment
Time Frame: Data will be collected at PET scan #1 (between days -28 and 0 before intervention) and at PET scan #2 during Week 12 of intervention
Secondary Outcomes
- Effect of minocycline exposure on self-rated anxiety and emotion regulation as measured by ADAMS (Anxiety and Depression Mood Scale)(Data will be collected at baseline and during Weeks 6 and 12 of intervention)
- Effect of minocycline exposure on cognition across seven cognitive domains before and after low dose intervention and regular dose intervention as measured by MCCB (MATRICS Consensus Cognitive Battery) subdomain scores(Data will be collected at baseline and during Weeks 6 and 12 of intervention)
- Effect of minocycline exposure on peripheral inflammatory cytokine profiles as measured by DNA and RNA expression in blood samples(Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12))