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Trial record 2 of 4 for:    minocycline and autism

Measuring Brain Inflammation in Autism

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Michael Gandal, MD, PhD, University of California, Los Angeles
Sponsor:
Information provided by (Responsible Party):
Michael Gandal, MD, PhD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT03117530
First received: November 30, 2016
Last updated: April 17, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Autism Spectrum Disorder Drug: Minocycline Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Targeting Microglial Activation for Treatment of Autism Spectrum Disorder (ASD): A Proof-of-Concept, Target-Engagement Study

Resource links provided by NLM:


Further study details as provided by Michael Gandal, MD, PhD, University of California, Los Angeles:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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) ]

Other Outcome Measures:
  • 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 ]
  • 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 ]
  • 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 ]

Estimated Enrollment: 30
Actual Study Start Date: April 1, 2017
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: minocin

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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. Capacity to consent to research
  5. 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
  11. Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03117530

Contacts
Contact: Michael Gandal, MD PhD 310-267-4798 autismresearch@ucla.edu

Locations
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Jenny Cowen    310-267-4798    autismresearch@ucla.edu   
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Michael Gandal, MD PhD University of California, Los Angeles
  More Information

Responsible Party: Michael Gandal, MD, PhD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03117530     History of Changes
Other Study ID Numbers: 16-001784
Study First Received: November 30, 2016
Last Updated: April 17, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD will not be shared

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

Keywords provided by Michael Gandal, MD, PhD, University of California, Los Angeles:
minocycline
brain inflammation
microglia
cognition

Additional relevant MeSH terms:
Autistic Disorder
Autism Spectrum Disorder
Minocycline
Child Development Disorders, Pervasive
Encephalitis
Neurodevelopmental Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 24, 2017