Study of Neuroimaging Biomarkers of Social Cognition Deficits in Adolescents (Age 13-17) With Autism Spectrum Disorder and Effects of Gabapentin
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|ClinicalTrials.gov Identifier: NCT03589898|
Recruitment Status : Recruiting
First Posted : July 18, 2018
Last Update Posted : July 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Autism Spectrum Disorder||Drug: Gabapentin||Early Phase 1|
The investigators will complete a 1H-MRS study in 70 adolescents with ASD. Given the low burden on patients, it is assumed that 90% of those recruited to participate in baseline 1H-MRS (Aim 1) will also consent/assent to repeated 1H-MRS after gabapentin administration (Aim 2). Projections from the preliminary study were used to select a proposed number of subjects that would be both achievable in the time frame of study and adequate to evaluate the research hypotheses.
Psychiatric comorbidity will be assessed based on DSM-5 criteria by clinical interview and administration of the Kiddie-Schedule for Affective Disorders and Schizophrenia (Present and Lifetime version; K-SADS-PL).
T1- and T2-weighted high resolution structural imaging (T1- and T2-weighted (MPRAGE)) will be acquired. These structural MRI scans will be analyzed using FreeSurfer (Martinos Center for Biomedical Imaging, Charlestown, MA) and Statistical Parameter Mapping (SPM8- http://www.fil.ion.ucl.ac.uk/spm/software/spm8/) to determine white matter, gray matter and CSF contributions to the MRS voxel for partial volume correction. This data will be analyzed for variation with age, and used as a co-variate in the statistical analysis plan.
MRS data will be acquired from the Anterior Cingulate Cortex and Occipital cortex. Imaging sessions will be conducted at the Advanced MRI Center (AMRIC) at UMMS, which houses a 3.0 Tesla Philips Achieva MRI research scanner (Philips Healthcare, Best, Netherlands) and 32-channel phase-array receiver SENSE head coil. AMRIC is dedicated to research and the MRI system has considerable evening and weekend availability. A Board certified neuroradiologist associated with the AMRIC at UMMS reviews all MRI scans. In the event of an unexpected, clinically important finding, the primary investigator will be informed. The investigator will share the finding with the participant and be in contact with the participant's primary care physician (PCP) in order to help decide the appropriate follow-up care/work up that is needed (consent will be obtained to contact each child's PCP during the study consent process).
GLU+GLN absolute levels will be quantified, and GABA levels will be quantified using the total creatine (tCr) peak as a reference. Macromolecule-suppressed editing will be used with MEGA-PRESS sequence, including prospective frequency correction to address the impact of drift and motion during scans.
Neurotransmitter levels will be correlated with social cognition measures. In females of reproductive age, menstrual cycle charting will be done for 2 months prior to scan, and imaging will be timed to target the mid-luteal phase, as cortical GABA levels fluctuate during the menstrual cycle and are most similar to levels in males during the luteal phase. In analysis of female subject data, menstrual phase will be confirmed on the day of the scan by measurement of serum estradiol and progesterone levels, and these levels will be used as covariates in the analysis. Exploratory analysis will be used to seek correlations with all clinical measures.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Imaging Biomarkers of Social Cognition and Pharmacologic Target Engagement in Autism Spectrum Disorder|
|Actual Study Start Date :||September 14, 2017|
|Estimated Primary Completion Date :||June 1, 2021|
|Estimated Study Completion Date :||June 1, 2021|
Single dose of gabapentin 900 mg will be given and neuroimaging markers will be measured before and after administration of gabapentin
Single dose of gabapentin 900 mg
- Cortical GABA in Anterior Cingulate Cortex [ Time Frame: 6 hours post-administration ]Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in bilateral anterior cingulate cortex
- Cortical GABA in Occipital Cortex [ Time Frame: 6 hours post-administration ]Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in bilateral occipital cortex
- Cortical Glx in Anterior Cingulate Cortex [ Time Frame: 6 hours post-administration ]Cortical glutamate/glutamine levels measured using magnetic resonance spectroscopy with voxel placed in bilateral anterior cingulate cortex
- Cortical Glx in Occipital Cortex [ Time Frame: 6 hours post-administration ]Cortical glutamate/glutamine levels measured using magnetic resonance spectroscopy with voxel placed in bilateral occipital cortex
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03589898
|Contact: David Cochran, MD, PhDfirstname.lastname@example.org|
|Contact: Ann Foley, BA||774-455-4103||Ann.Foley@umassmed.edu|
|United States, Massachusetts|
|University of Massachusetts Medical School||Recruiting|
|Worcester, Massachusetts, United States, 01655|
|Contact: Taylor Sacco, BA 774-455-4100 Taylor.Sacco@umassmed.edu|
|Contact: Ann Foley, BA 774-455-4103 Ann.Foley@umassmed.edu|
|Principal Investigator:||David Cochran, MD, PhD||University of Massachusetts, Worcester|