Autism Spectrum DisorderEarly Phase 1NCT03589898
Study of Neuroimaging Biomarkers of Social Cognition Deficits in Adolescents (Age 13-17) With Autism Spectrum Disorder and Effects of Gabapentin
A Early Phase 1 study testing Gabapentin in people with Autism Spectrum Disorder, run by University of Massachusetts, Worcester at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 17 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Gabapentin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2017to 31 Aug 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
About this study
Official title: Imaging Biomarkers of Social Cognition and Pharmacologic Target Engagement in Autism Spectrum Disorder
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.
Read the 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.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Gabapentin
- Keywords
- magnetic resonance imaging, spectroscopy, GABA, glutamate, social cognition
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GabapentinDrug
Single dose of gabapentin 900 mg
| Study group | Role | What they receive |
|---|---|---|
| Gabapentin | Experimental | Single dose of gabapentin 900 mg will be given and neuroimaging markers will be measured before and after administration of gabapentin Receives: Drug: Gabapentin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortical GABA in Anterior Cingulate Cortex
Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in bilateral anterior cingulate cortex
Measured: 6 hours post-administration
Cortical GABA in Right Anterior Insula
Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in right anterior insula
Measured: 6 hours post-administration
Secondary outcomes (2)
Cortical Glx in Anterior Cingulate Cortex
Cortical glutamate/glutamine levels measured using magnetic resonance spectroscopy with voxel placed in bilateral anterior cingulate cortex
Measured: 6 hours post-administration
Cortical Glx in Right Anterior Insula
Cortical glutamate/glutamine levels measured using magnetic resonance spectroscopy with voxel placed in right anterior insula
Measured: 6 hours post-administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start14 Sep 2017
- Primary completion31 Aug 2022
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Cochran, University of Massachusetts, Worcester
- Investigators
- David Cochran, MD, PhD, Principal investigator, University of Massachusetts, Worcester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03589898
- Sponsor's protocol ID
- H00012656
- Other IDs
- 1K23MH113008-01A1
- Status last verified
- Oct 2022
- First submitted
- 6 Jul 2018
- Last updated
- 2 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Plan for sharing individual participant data is still being discussed and developed by study team.
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging Biomarkers of Social Cognition and Pharmacologic Target Engagement in Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT03589898
- Acronym / sponsor ID
- H00012656
- Conditions
- Autism Spectrum Disorder
- Keywords
- magnetic resonance imaging, spectroscopy, GABA, glutamate, social cognition
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Johns Hopkins University
- Study start
- 14 Sep 2017 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 18 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gabapentin | Experimental | Drug: GabapentinSingle dose of gabapentin 900 mg will be given and neuroimaging markers will be measured before and after administration of gabapentin |
Who may qualify
- Ages
- 13 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GabapentinSingle dose of gabapentin 900 mg | Drug | Gabapentin |
Primary outcome
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 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
2 secondary outcomes
Cortical Glx in Anterior Cingulate Cortex
Time frame: 6 hours post-administration
Cortical Glx in Right Anterior Insula
Time frame: 6 hours post-administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
- Individual participant dataSharing planned: Undecided. Plan for sharing individual participant data is still being discussed and developed by study team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Cochran, MD, PhD principal investigator
University of Massachusetts, Worcester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Gabapentin in people with Autism Spectrum Disorder, run by University of Massachusetts, Worcester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortical GABA in Anterior Cingulate Cortex (time frame: 6 hours post-administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2022.