- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03589898
Study of Neuroimaging Biomarkers of Social Cognition Deficits in Adolescents (Age 13-17) With Autism Spectrum Disorder and Effects of Gabapentin
Imaging Biomarkers of Social Cognition and Pharmacologic Target Engagement in Autism Spectrum Disorder
Study Overview
Detailed Description
The investigators will complete a 1H-MRS study in 42 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 Right anterior insula. 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
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Worcester, Massachusetts, United States, 01655
- University of Massachusetts Medical School
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 13-17 years
- English as primary language (both child and legal guardian)
- DSM-5 criteria for Autism Spectrum Disorder
- IQ >70 per Weschler Abbreviated Scale of Intelligence (WASI)
- Informed assent for the study (The guardian must also give written informed consent).
Exclusion Criteria:
- Any neurological disorder (e.g., cerebral palsy, fetal alcohol syndrome, cerebral neoplasm, bacterial meningitis, epilepsy, etc.)
- Genetic disorders (e.g., Fragile X, Rett Syndrome, etc.)
- Preterm (<36 weeks)
- Failure to thrive within first year of life
- Contraindications for MRI, such as metallic or electronic implants in the body, or severe claustrophobia
- History of head trauma with loss of consciousness for more than 30 minutes
- Unstable psychiatric illness, history of psychotic disorder, or psychiatric illness that would prevent the subject from being able to complete study protocol
- Unstable medical illness such as diabetes, asthma, thyroid disease.
- Currently on medications that cause respiratory depression, e.g. opioids, benzodiazepines
- Clinically significant suicidal ideation at screening as assessed by the Columbia Suicide Severity Rating Scale
- IQ < 70
- History of intolerance to gabapentin or pregabalin
- Current substance use (including nicotine)
- Pregnancy at time of 1H-MRS or gabapentin administration
- Current treatment with gabapentin
- History of Renal Dysfunction
- Subjects who weigh less than 36 kg
- Subjects who weigh more than 105.8 kg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Gabapentin
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
6 hours post-administration
|
Cortical GABA in Right Anterior Insula
Time Frame: 6 hours post-administration
|
Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in right anterior insula
|
6 hours post-administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
6 hours post-administration
|
Cortical Glx in Right Anterior Insula
Time Frame: 6 hours post-administration
|
Cortical glutamate/glutamine levels measured using magnetic resonance spectroscopy with voxel placed in right anterior insula
|
6 hours post-administration
|
Collaborators and Investigators
Investigators
- Principal Investigator: David Cochran, MD, PhD, University of Massachusetts, Worcester
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Neurodevelopmental Disorders
- Autistic Disorder
- Autism Spectrum Disorder
- Child Development Disorders, Pervasive
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Anti-Anxiety Agents
- Anticonvulsants
- Antimanic Agents
- Gabapentin
Other Study ID Numbers
- H00012656
- 1K23MH113008-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Autism Spectrum Disorder
-
Stanford UniversityCalifornia Department of Developmental ServicesRecruitingAutism Spectrum Disorder | Autistic Disorder | Autism | Autism Spectrum Disorders | Autistic Disorders Spectrum | Autistic Spectrum Disorder | Autistic Spectrum DisordersUnited States
-
Hoffmann-La RocheActive, not recruitingAutism Spectrum Disorder (ASD)United States, Canada, Italy, Spain
-
Axial Therapeutics, Inc.Active, not recruitingAutism Spectrum Disorder (ASD)United States, Australia, New Zealand
-
Technion, Israel Institute of TechnologyCompleted
-
Stanford UniversityNational Institute on Deafness and Other Communication Disorders (NIDCD)CompletedAutism | Autism Spectrum Disorder (ASD)United States
-
Corporacion Parc TauliUnknown
-
Institut de Recherches Internationales ServierADIR, a Servier Group companyTerminatedAutism Spectrum Disorder (ASD)Spain, United States, Hungary, Poland, Australia, United Kingdom, Brazil, Czechia, France, Italy, Portugal, Slovakia
-
Florida Gulf Coast UniversityCompletedAutism Spectrum Disorder High-FunctioningUnited States
-
Hospital Universitario Dr. Jose E. GonzalezUnknownAutism | Autism SpectrumMexico
-
National Taiwan University HospitalCompletedAutism Spectrum Disorder High-FunctioningTaiwan
Clinical Trials on Gabapentin
-
University Hospital, GhentAmsterdam UMC, location VUmc; University GhentCompletedEpilepsy and Neuropathic PainBelgium
-
Samuel Lunenfeld Research Institute, Mount Sinai...Completed
-
Mayo ClinicCompleted
-
Viatris Specialty LLCCompletedAbuse PotentialUnited States
-
University of KarachiCenter for Bioequivalence Studies and Clinical Research; Merck Pvt. Ltd, PakistanCompletedHealthy Volunteers | Bioequivalence StudyPakistan
-
Indiana UniversityCompletedPostoperative PainUnited States
-
Celgene CorporationCompletedBreast Neoplasms | Metastases, NeoplasmUnited States
-
Celgene CorporationCompletedNeoplasms | Metastases, NeoplasmUnited States
-
XenoPort, Inc.Completed
-
Endo PharmaceuticalsCompletedCarpal Tunnel Syndrome | Complex Regional Pain Syndrome | Peripheral Neuropathy | Diabetic Neuropathy | Postherpetic Neuralgia | HIV Neuropathy | Idiopathic Sensory NeuropathyUnited States