Measuring Brain Inflammation in Autism

NCT ID: NCT03117530

Last Updated: 2020-08-10

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-11
• Study Completion Date: 2022-12-31

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.

Conditions

Autism Spectrum Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Minocycline

Group Type: EXPERIMENTAL

Minocycline

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

minocin

Eligibility Criteria

Inclusion Criteria

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)

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Michael Gandal, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Gandal, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

UCLA

Los Angeles, California, United States

Countries

United States

Other Identifiers

16-001784

Identifier Type: -

Identifier Source: org_study_id