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Trial record 93 of 257 for:    Recruiting, Not yet recruiting, Available Studies | "Autistic Disorder"

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 19, 2018
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Johns Hopkins University
Information provided by (Responsible Party):
David Cochran, University of Massachusetts, Worcester

Brief Summary:
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is increasing in prevalence, and is characterized by deficits in social communication and interaction across multiple contexts, and restricted, repetitive patterns of behavior, interests, or activities. The majority of individuals with ASD have poor outcomes in the area of social functioning; however, there are no medical treatments available that target the core social communication deficits. The goal of the proposed research is to understand the neurobiological role of an imbalance in excitatory (glutamate) and inhibitory (gamma-aminobutyric acid, GABA) neurotransmission in the social cognition deficits in ASD, and to develop proton magnetic resonance spectroscopy as a measurement of target engagement to measure the ability of a medication, gabapentin, to increase cortical GABA levels. Spectrally-edited proton magnetic resonance spectroscopy (1H-MRS) provides an ideal method for measuring cortical GABA levels. All proposed studies will be in 70 adolescents (male and female) with ASD (age 13 to 17 years). Specific Aim 1: To measure correlations of 1H-MRS GABA levels in the anterior cingulate cortex (ACC) and occipital cortex (OC) with clinical measures of social cognition at baseline. Specific Aim 2: To measure the effect of an initial one time dose of gabapentin on 1H-MRS GABA levels in the ACC and OC. The hypotheses are 1) that higher social cognition ability will be positively correlated with GABA in the ACC but not in the OC (a control, non-social cognition-related region) of individuals with ASD, and 2) that gabapentin will increase GABA levels in the ACC and OC of youth with ASD.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Drug: Gabapentin Early Phase 1

Detailed Description:

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)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine


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
Drug: Gabapentin
Single dose of gabapentin 900 mg




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 13-17 years
  2. English as primary language (both child and legal guardian)
  3. DSM-5 criteria for Autism Spectrum Disorder
  4. IQ >85 per Weschler Abbreviated Scale of Intelligence (WASI)
  5. Informed assent for the study (The guardian must also give written informed consent).

Exclusion Criteria:

  1. Any neurological disorder (e.g., cerebral palsy, fetal alcohol syndrome, cerebral neoplasm, bacterial meningitis, epilepsy, etc.)
  2. Genetic disorders (e.g., Fragile X, Rett Syndrome, etc.)
  3. Preterm (<36 weeks)
  4. Failure to thrive within first year of life
  5. Contraindications for MRI, such as metallic or electronic implants in the body, or severe claustrophobia
  6. History of head trauma with loss of consciousness for more than 30 minutes
  7. Unstable psychiatric illness, history of psychotic disorder, or psychiatric illness that would prevent the subject from being able to complete study protocol
  8. Clinically significant suicidal ideation as assessed by the Columbia Suicide Severity Rating Scale
  9. IQ < 85
  10. History of intolerance to gabapentin or pregabalin
  11. Current substance use (including nicotine)
  12. Pregnancy at time of 1H-MRS or gabapentin administration
  13. Current treatment with gabapentin
  14. History of Renal Dysfunction
  15. Changes in any psychotrophic medication within 4 weeks prior to screening (8 weeks for changes in fluoxetine dosing), and subjects will be removed from study if medication changes are made between screening and the completion of protocol
  16. Subjects who weigh less than 25 kg

Information from the National Library of Medicine

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


Contacts
Contact: David Cochran, MD, PhD 508-856-5096 david.cochran@umassmemorial.org
Contact: Ann Foley, BA 774-455-4103 Ann.Foley@umassmed.edu

Locations
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   
Sponsors and Collaborators
University of Massachusetts, Worcester
National Institute of Mental Health (NIMH)
Johns Hopkins University
Investigators
Principal Investigator: David Cochran, MD, PhD University of Massachusetts, Worcester

Responsible Party: David Cochran, Assistant Professor of Psychiatry and Pediatrics, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT03589898     History of Changes
Other Study ID Numbers: H00012656
1K23MH113008-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Plan for sharing individual participant data is still being discussed and developed by study team.

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.: No

Keywords provided by David Cochran, University of Massachusetts, Worcester:
magnetic resonance imaging
spectroscopy
GABA
glutamate
social cognition

Additional relevant MeSH terms:
Autistic Disorder
Autism Spectrum Disorder
Disease
Child Development Disorders, Pervasive
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders
Gabapentin
gamma-Aminobutyric Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Antimanic Agents
GABA Agents