- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03117530
Measuring Brain Inflammation in Autism
August 6, 2020 updated by: Michael Gandal, MD, PhD, University of California, Los Angeles
Targeting Microglial Activation for Treatment of Autism Spectrum Disorder (ASD): A Proof-of-Concept, Target-Engagement Study
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.
Study Overview
Study Type
Interventional
Enrollment (Anticipated)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 33 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion criteria for participants with ASD
- Male with a diagnosis of ASD as defined by DSM-5, confirmed by clinical evaluation and ADOS-2.
- Age 18-35 years inclusive
- IQ estimate of >70 on VIQ or PIQ
- Capacity to consent to research
- Ability to comply with all protocol procedures and assessments
- Availability of an informant willing to provide information regarding subject behavior and health status (Note: Informant role requires a responsible adult with close, ongoing contact and knowledge of the subject; parent/caregiver acceptable, but not necessary for role)
Exclusion criteria for participants with ASD
- Evidence of current nicotine, drug, or alcohol abuse or dependence
- Presence of a chronic medical condition which would potentially influence the assessment of TSPO binding, or interact with study medication (eg. hepatic, neurologic, renal disease) to increase risk to the subject
- Presence of severe behavioral disturbance likely to require initiation of treatment during the course of the protocol
- Clinical judgment of the study physician of inability to perform the requirements of the study
- Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, or benzodiazepines
- Homozygous genotype for minor allele of rs6971
- History of recent febrile illness in past 30 days
- History of allergic reactions to tetracycline antibiotics
- Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change
- Current prescribed medication likely to confound assessment of TSPO binding
Inclusion criteria for healthy volunteer participants
- Male in good general health, confirmed by clinical evaluation
- Age 18-35 years inclusive
- IQ estimate of >70 on VIQ or PIQ
- Ability to comply with all protocol procedures and assessments
Exclusion criteria for healthy volunteer participants
- Diagnosis of an autism spectrum disorder (ASD)
- Evidence of current nicotine, drug, or alcohol abuse or dependence
- Presence of a chronic medical condition which would potentially influence the assessment of TSPO binding, or interact with study medication (eg. hepatic, neurologic, renal disease) to increase risk to the subject
- Presence of current or lifetime severe psychopathology potentially confounding assessment of TSPO binding (psychosis, severe depression, bipolar disorder, Obsessive-Compulsive Disorder)
- Current prescribed medication likely to confound assessment of TSPO binding
- Clinical judgment of the study physician of inability to perform the requirements of the study
- Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, benzodiazepines, or psychotropic medications likely to confound assessment of TSPO binding
- Homozygous genotype for minor allele of rs6971
- SRS-2 T-score score of >59
- History of recent febrile illness in past 30 days
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Minocycline
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Following initial baseline PET-CT imaging and clinical evaluation, adults with ASD will undergo a 12- week open-label treatment trial of minocycline to be conducted at UCLA under supervision of the UCLA IRB.
During weeks 1-6, ASD subjects will be treated with 50 mg minocycline twice daily (low dose).
From weeks 7-12, dosing will be increased to 100mg twice daily (typical clinical dosage).
Every two weeks during this phase, a treating clinician will measure vital signs, assess safety, record adverse effects, and monitor compliance.
Compliance will be obtained as an index of tolerability and will assessed through weekly medication diaries and pill counts.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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Data will be collected at PET scan #1, which will take place during screening (Days -28 to 0) for the study
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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
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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
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: Data will be collected at baseline and during Weeks 6 and 12 of intervention
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Data will be collected at baseline and during Weeks 6 and 12 of intervention
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Effect of minocycline exposure on self-rated anxiety and emotion regulation as measured by ADAMS (Anxiety and Depression Mood Scale)
Time Frame: Data will be collected at baseline and during Weeks 6 and 12 of intervention
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Data will be collected at baseline and during Weeks 6 and 12 of intervention
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Effect of minocycline exposure on peripheral inflammatory cytokine profiles as measured by DNA and RNA expression in blood samples
Time Frame: Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)
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Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in clinician-rated global improvement as measured by CGI
Time Frame: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention
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Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention
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Change in self-reported symptoms of ASD with minocycline treatment as measured by SRS-2
Time Frame: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention
|
Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention
|
Change in informant-reported symptoms of ASD with minocycline treatment as measured by ABC-CV
Time Frame: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention
|
Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Michael Gandal, MD PhD, University of California, Los Angeles
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 11, 2017
Primary Completion (Anticipated)
December 1, 2022
Study Completion (Anticipated)
December 1, 2022
Study Registration Dates
First Submitted
November 30, 2016
First Submitted That Met QC Criteria
April 17, 2017
First Posted (Actual)
April 18, 2017
Study Record Updates
Last Update Posted (Actual)
August 10, 2020
Last Update Submitted That Met QC Criteria
August 6, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16-001784
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
IPD Plan Description
IPD will not be shared
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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