Autism Spectrum DisorderPhase 1NCT03117530
Measuring Brain Inflammation in Autism
A Phase 1 study testing Minocycline in people with Autism Spectrum Disorder, run by University of California, Los Angeles at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Apr 2017to Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Minocycline
- Keywords
- minocycline, brain inflammation, microglia, cognition
- Medical subject headings
- Autism Spectrum Disorder, cyclopia sequence, Encephalitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called minocin
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.
| Study group | Role | What they receive |
|---|---|---|
| Minocycline | Experimental | Not described Receives: Drug: Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate differences in CNS microglial activation in adults with ASD versus healthy volunteers via in vivo CNS binding of [11C]-DAA1106
Measured: 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
Measured: 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 (3)
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
Measured: 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)
Measured: 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
Measured: Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start11 Apr 2017
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: COVID
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Gandal, MD, PhD, University of California, Los Angeles
- Investigators
- Michael Gandal, MD PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03117530
- Sponsor's protocol ID
- 16-001784
- Status last verified
- Aug 2020
- First submitted
- 30 Nov 2016
- Last updated
- 10 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Microglial Activation for Treatment of Autism Spectrum Disorder (ASD): A Proof-of-Concept, Target-Engagement Study
- ClinicalTrials.gov ID
- NCT03117530
- Acronym / sponsor ID
- 16-001784
- Conditions
- Autism Spectrum Disorder
- Keywords
- minocycline, brain inflammation, microglia, cognition
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: COVID
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 11 Apr 2017 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 18 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Minocycline | Experimental | Drug: Minocycline |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAlso: minocinFollowing 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. | Drug | Minocycline |
Primary outcome
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
3 secondary outcomes
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
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
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2020.
- Individual participant dataSharing planned: No. IPD will not be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Gandal, MD PhD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Minocycline in people with Autism Spectrum Disorder, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 10 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2020.