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

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 31 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion criteria for participants with ASD

  1. Male with a diagnosis of ASD as defined by DSM-5, confirmed by clinical evaluation and ADOS-2.
  2. Age 18-35 years inclusive
  3. IQ estimate of >70 on VIQ or PIQ
  4. Capacity to consent to research
  5. Ability to comply with all protocol procedures and assessments
  6. 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

  1. Evidence of current nicotine, drug, or alcohol abuse or dependence
  2. 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
  3. Presence of severe behavioral disturbance likely to require initiation of treatment during the course of the protocol
  4. Clinical judgment of the study physician of inability to perform the requirements of the study
  5. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, or benzodiazepines
  6. Homozygous genotype for minor allele of rs6971
  7. History of recent febrile illness in past 30 days
  8. History of allergic reactions to tetracycline antibiotics
  9. Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change
  10. Current prescribed medication likely to confound assessment of TSPO binding

Inclusion criteria for healthy volunteer participants

  1. Male in good general health, confirmed by clinical evaluation
  2. Age 18-35 years inclusive
  3. IQ estimate of >70 on VIQ or PIQ
  4. Ability to comply with all protocol procedures and assessments

Exclusion criteria for healthy volunteer participants

  1. Diagnosis of an autism spectrum disorder (ASD)
  2. Evidence of current nicotine, drug, or alcohol abuse or dependence
  3. 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
  4. Presence of current or lifetime severe psychopathology potentially confounding assessment of TSPO binding (psychosis, severe depression, bipolar disorder, Obsessive-Compulsive Disorder)
  5. Current prescribed medication likely to confound assessment of TSPO binding
  6. Clinical judgment of the study physician of inability to perform the requirements of the study
  7. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, benzodiazepines, or psychotropic medications likely to confound assessment of TSPO binding
  8. Homozygous genotype for minor allele of rs6971
  9. SRS-2 T-score score of >59
  10. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Minocycline
Drug: Minocycline
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:
  • minocin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
Data will be collected at baseline and during Weeks 6 and 12 of intervention
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
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
Time Frame: Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)
Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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
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 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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, Los Angeles

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 11, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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