Autism DisorderEarly Phase 1NCT02278328
MEG Study of Acute STX209 Effects in ASD
A Early Phase 1 study testing STX209 (15mg) and STX209 (30mg) in people with Autism Disorder, run by Timothy Roberts at 1 site in United States.
Trial summary
This is a single-site, randomized, acute dose-response study to determine whether STX209 produces a dose-dependent significant change in MEG target parameters compared to baseline as well as compared to placebo treatment. Read more about this study
- Who is it for?
- Ages 14 to 17 years, men only
- Conditions the study is for
- Autism Disorder
- What is being tested?
- STX209 (15mg) and STX209 (30mg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to 27 Sep 2019
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 14 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Right- handed males aged 14 to 17.75 years.
- Diagnosis of ASD with the last 12 months according to the DSM-IV criteria, including Autistic Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), and Asperger's Syndrome but excluding Childhood Dis-integrative Disorder and Rett Syndrome.
- Current pharmacological treatment regimen has been stable for at least 4 weeks prior to Screening.
- If the subject is already receiving stable non-pharmacological educational, behavioral, and/or dietary interventions, participation in these programs must have been continuous during the 2 months prior to Screening and subjects or their parent/caregiver may not electively initiate new or modify ongoing interventions for the duration of the study. Typical school vacations are not considered modifications of stable programming.
- Prior to the conduct of any study-specific procedures, the subject must provide verbal assent to participate in the study (if developmentally appropriate), and the parent/caregiver must provide written informed consent. If the caregiver attending the clinic visits is not the parent, written consent must be obtained from the parent for the caregiver's participation in the study.
Who cannot join
- No known neurological impairment (e.g., head trauma with loss of consciousness for more than 10 minutes, stroke, seizure disorder).
- Claustrophobia
- Metallic implanted prosthetic or stimulation device (including pacemaker)
- Excessive metallic dental work (including braces, non-removable retainers)
- Subjects who are currently receiving treatment with racemic baclofen, vigabatrin, tiagabine, or riluzole.
- Subjects who have taken another investigational drug within the last 30 days.
Show all 9Show fewer
- Subjects who are not able to take oral medications.
- Subjects who have a history of hypersensitivity to racemic baclofen.
- Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Phladelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Magnetoencephalography / Magnetic Resonance Spectroscopy Dose Response Study of Arbaclofen in Autism Spectrum Disorder
This is a single-site, randomized, acute dose-response study to determine whether STX209 produces a dose-dependent significant change in MEG target parameters compared to baseline as well as compared to placebo treatment.
Read the detailed description
Recent evidence from magnetoencephalographic (MEG) studies in ASD have pointed to abnormalities (specifically, delays) in auditory evoked neuromagnetic responses (e.g. M100 - see Roberts et al., 2010, and mismatch field, MMF - see Roberts et al., 2011) as well as abnormalities in the oscillatory behavior of auditory cortex, especially in the gamma band (30-50Hz), at rest and in response to simple auditory stimuli (see Gandal et al., 2010 and Cornew et al., 2012; Edgar et al., 2013). The local circuitry underlying such evoked activity and oscillations, and synaptic transmission in general, requires an appropriate balance of excitation and inhibition, mediated by glutamate and GABA, respectively. One model of the neural oscillatory deficits in ASD suggests that impaired regulatory control by inhibitory interneurons onto pyramidal cells underlies abnormal auditory latency and oscillatory electrophysiological measures. As such, electrophysiological deficits are interpreted in terms of local circuitry abnormalities, with inferences at the molecular level of imbalances in the activity of glutamate and GABA.
A candidate therapeutic for ASD has been developed - STX209, a GABA-B agonist. Since this pharmaceutical targets synaptic activity that has clear electrophysiological correlates, one goal of this proposal is to assess the responsiveness (sensitivity to change) of MEG measures to acute administration of STX209 at various doses in adolescents on the autism spectrum. The study also aims to establish the nature of the putative relationship between such electrophysiologic markers and GABA and glutamate levels using MEGAPRESS spectrally-edited magnetic resonance spectroscopy (MRS).
- Conditions
- Autism Disorder
- Being tested
- STX209 (15mg), placebo, STX209 (30mg)
- Keywords
- dose titration study, electrophysiology
- Medical subject headings
- Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STX209 (15mg)Drug
Also called Arbaclofen (15mg)
A randomized acute dose-response design will be employed with a total study duration of 3 weeks. At each visit, baseline MEG will be obtained followed by acute single-dose drug/placebo administration, followed 60 minutes later by repeat MEG. Each participant will receive a single dose of placebo in random order and a single dose of STX209 from smallest to largest (15mg, and 30mg). MRI and MRS will be performed immediately following MEG to provide an anatomic basis for source localization as well as to assess acute effects of STX209 administration on MRS estimates of GABA and glutamate. The STX209 (15mg) intervention is the "low dose"
placeboDrug
A randomized acute dose-response design will be employed with a total study duration of 3 weeks. At each visit, baseline MEG will be obtained followed by acute single-dose drug/placebo administration, followed 60 minutes later by repeat MEG. Each participant will receive a single dose of placebo in random order and a single dose of STX209 from smallest to largest (15mg, and 30mg). MRI and MRS will be performed immediately following MEG to provide an anatomic basis for source localization as well as to assess acute effects of STX209 administration on MRS estimates of GABA and glutamate. The placebo intervention is the non-active placebo control dose
STX209 (30mg)Drug
Also called Arbaclofen (30mg)
A randomized acute dose-response design will be employed with a total study duration of 3 weeks. At each visit, baseline MEG will be obtained followed by acute single-dose drug/placebo administration, followed 60 minutes later by repeat MEG. Each participant will receive a single dose of placebo in random order and a single dose of STX209 from smallest to largest (15mg, and 30mg). MRI and MRS will be performed immediately following MEG to provide an anatomic basis for source localization as well as to assess acute effects of STX209 administration on MRS estimates of GABA and glutamate. The STX209 (30mg) intervention is the "high dose"
| Study group | Role | What they receive |
|---|---|---|
| A. Placebo then 15mg then 30mg | Experimental | Subjects will receive a single dose of placebo on week 1, 15 mg of STX209 on week 2 and 30 mg of STX209 on week 3.
Subjects will receive STX209 via oral disintegrating tablets, administered in individual 15mg tablets. Receives: Drug: STX209 (15mg); Drug: placebo; Drug: STX209 (30mg) |
| B. 15mg then placebo then 30mg | Experimental | Subjects will receive a single dose of 15 mg of STX209 on week 1, placebo on week 2 and 30 mg of STX209 on week 3.
Subjects will receive STX209 via oral disintegrating tablets, administered in individual 15mg tablets. Receives: Drug: STX209 (15mg); Drug: placebo; Drug: STX209 (30mg) |
| C. 15mg then 30mg then placebo | Experimental | Subjects will receive a single dose of 15 mg of STX209 on week 1, 30 mg of STX209 on week 2 and placebo on week 3.
Subjects will receive STX209 via oral disintegrating tablets, administered in individual 15mg tablets. Receives: Drug: STX209 (15mg); Drug: placebo; Drug: STX209 (30mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
M50 Latency (Left Hemisphere)
The latency of the M50 auditory evoked response component arising from the left cerebral hemisphere
Measured: 1 hour per intervention followed by a 1 week washout for a total of three weeks
M50 Latency (Right Hemisphere)
The latency of the M50 auditory evoked response component arising from the right cerebral hemisphere
Measured: 1 hour per intervention followed by a 1 week washout for a total of three weeks
Steady State Inter Trial Coherence (Left Hemisphere)
The inter trial coherence (ITC) of auditory steady state response arising from the left cerebral hemisphere
Measured: 1 hour per intervention followed by a 1 week washout for a total of three weeks
Steady State Inter Trial Coherence (Right Hemisphere)
The inter trial coherence (ITC) of auditory steady state response arising from the right cerebral hemisphere
Measured: 1 hour per intervention followed by a 1 week washout for a total of three weeks
GABA (Left Hemisphere)
GABA/Cr ratio arising from a voxel in the left superior temporal gyrus
Measured: 1 hour per intervention followed by a 1 week washout for a total of three weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2014 (estimated)
- Study startFeb 2016
- Primary completion30 Jul 2018
- Study completion27 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autism DisorderStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All subjects receive placebo and two separate doses of STX209 (15mg, 30mg). The order of administration of these (at weekly intervals) is randomized into groups: (A) placebo, 15, 30 ; (B) 15, placebo, 30 and (C) 15, 30, placebo.
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Timothy Roberts
- Sponsor type
- University, hospital or other
- Collaborators
- Simons Foundation, Clinical Research Associates, LLC
- Responsible party
- Sponsor-investigator, Timothy Roberts, Children's Hospital of Philadelphia
- Investigators
- Timothy Roberts, PhD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02278328
- Sponsor's protocol ID
- 14-010857
- Status last verified
- Sep 2019
- First submitted
- 17 Oct 2014
- Last updated
- 21 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetoencephalography / Magnetic Resonance Spectroscopy Dose Response Study of Arbaclofen in Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT02278328
- Acronym / sponsor ID
- 14-010857
- Conditions
- Autism Disorder
- Keywords
- dose titration study, electrophysiology
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Timothy RobertsUniversity, hospital or other
- Collaborators
- Simons Foundation, Clinical Research Associates, LLC
- Study start
- Feb 2016
- Primary completion
- 30 Jul 2018 (actual)
- Study completion
- 27 Sep 2019 (actual)
- First posted
- 30 Oct 2014 (estimated)
- Results
- Posted 21 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-site, randomized, acute dose-response study to determine whether STX209 produces a dose-dependent significant change in MEG target parameters compared to baseline as well as compared to placebo treatment.
Detailed description
Recent evidence from magnetoencephalographic (MEG) studies in ASD have pointed to abnormalities (specifically, delays) in auditory evoked neuromagnetic responses (e.g. M100 - see Roberts et al., 2010, and mismatch field, MMF - see Roberts et al., 2011) as well as abnormalities in the oscillatory behavior of auditory cortex, especially in the gamma band (30-50Hz), at rest and in response to simple auditory stimuli (see Gandal et al., 2010 and Cornew et al., 2012; Edgar et al., 2013). The local circuitry underlying such evoked activity and oscillations, and synaptic transmission in general, requires an appropriate balance of excitation and inhibition, mediated by glutamate and GABA, respectively. One model of the neural oscillatory deficits in ASD suggests that impaired regulatory control by inhibitory interneurons onto pyramidal cells underlies abnormal auditory latency and oscillatory electrophysiological measures. As such, electrophysiological deficits are interpreted in terms of local circuitry abnormalities, with inferences at the molecular level of imbalances in the activity of glutamate and GABA.
A candidate therapeutic for ASD has been developed - STX209, a GABA-B agonist. Since this pharmaceutical targets synaptic activity that has clear electrophysiological correlates, one goal of this proposal is to assess the responsiveness (sensitivity to change) of MEG measures to acute administration of STX209 at various doses in adolescents on the autism spectrum. The study also aims to establish the nature of the putative relationship between such electrophysiologic markers and GABA and glutamate levels using MEGAPRESS spectrally-edited magnetic resonance spectroscopy (MRS).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- All subjects receive placebo and two separate doses of STX209 (15mg, 30mg). The order of administration of these (at weekly intervals) is randomized into groups: (A) placebo, 15, 30 ; (B) 15, placebo, 30 and (C) 15, 30, placebo.
| Arm | Type | Receives |
|---|---|---|
| A. Placebo then 15mg then 30mg | Experimental | Drug: STX209 (15mg), Drug: placebo, Drug: STX209 (30mg)Subjects will receive a single dose of placebo on week 1, 15 mg of STX209 on week 2 and 30 mg of STX209 on week 3. Subjects will receive STX209 via oral disintegrating tablets, administered in individual 15mg tablets. |
| B. 15mg then placebo then 30mg | Experimental | Drug: STX209 (15mg), Drug: placebo, Drug: STX209 (30mg)Subjects will receive a single dose of 15 mg of STX209 on week 1, placebo on week 2 and 30 mg of STX209 on week 3. Subjects will receive STX209 via oral disintegrating tablets, administered in individual 15mg tablets. |
| C. 15mg then 30mg then placebo | Experimental | Drug: STX209 (15mg), Drug: placebo, Drug: STX209 (30mg)Subjects will receive a single dose of 15 mg of STX209 on week 1, 30 mg of STX209 on week 2 and placebo on week 3. Subjects will receive STX209 via oral disintegrating tablets, administered in individual 15mg tablets. |
Who may qualify
- Ages
- 14 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Right- handed males aged 14 to 17.75 years.
- Diagnosis of ASD with the last 12 months according to the DSM-IV criteria, including Autistic Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), and Asperger's Syndrome but excluding Childhood Dis-integrative Disorder and Rett Syndrome.
- Current pharmacological treatment regimen has been stable for at least 4 weeks prior to Screening.
- If the subject is already receiving stable non-pharmacological educational, behavioral, and/or dietary interventions, participation in these programs must have been continuous during the 2 months prior to Screening and subjects or their parent/caregiver may not electively initiate new or modify ongoing interventions for the duration of the study. Typical school vacations are not considered modifications of stable programming.
- Prior to the conduct of any study-specific procedures, the subject must provide verbal assent to participate in the study (if developmentally appropriate), and the parent/caregiver must provide written informed consent. If the caregiver attending the clinic visits is not the parent, written consent must be obtained from the parent for the caregiver's participation in the study.
Key exclusion criteria (9 listed)
- No known neurological impairment (e.g., head trauma with loss of consciousness for more than 10 minutes, stroke, seizure disorder).
- Claustrophobia
- Metallic implanted prosthetic or stimulation device (including pacemaker)
- Excessive metallic dental work (including braces, non-removable retainers)
- Subjects who are currently receiving treatment with racemic baclofen, vigabatrin, tiagabine, or riluzole.
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 |
|---|---|---|
| STX209 (15mg)Also: Arbaclofen (15mg)A randomized acute dose-response design will be employed with a total study duration of 3 weeks. At each visit, baseline MEG will be obtained followed by acute single-dose drug/placebo administration, followed 60 minutes later by repeat MEG. Each participant will receive a single dose of placebo in random order and a single dose of STX209 from smallest to largest (15mg, and 30mg). MRI and MRS will be performed immediately following MEG to provide an anatomic basis for source localization as well as to assess acute effects of STX209 administration on MRS estimates of GABA and glutamate. The STX209 (15mg) intervention is the "low dose" | Drug | A. Placebo then 15mg then 30mg, B. 15mg then placebo then 30mg, C. 15mg then 30mg then placebo |
| placeboA randomized acute dose-response design will be employed with a total study duration of 3 weeks. At each visit, baseline MEG will be obtained followed by acute single-dose drug/placebo administration, followed 60 minutes later by repeat MEG. Each participant will receive a single dose of placebo in random order and a single dose of STX209 from smallest to largest (15mg, and 30mg). MRI and MRS will be performed immediately following MEG to provide an anatomic basis for source localization as well as to assess acute effects of STX209 administration on MRS estimates of GABA and glutamate. The placebo intervention is the non-active placebo control dose | Drug | A. Placebo then 15mg then 30mg, B. 15mg then placebo then 30mg, C. 15mg then 30mg then placebo |
| STX209 (30mg)Also: Arbaclofen (30mg)A randomized acute dose-response design will be employed with a total study duration of 3 weeks. At each visit, baseline MEG will be obtained followed by acute single-dose drug/placebo administration, followed 60 minutes later by repeat MEG. Each participant will receive a single dose of placebo in random order and a single dose of STX209 from smallest to largest (15mg, and 30mg). MRI and MRS will be performed immediately following MEG to provide an anatomic basis for source localization as well as to assess acute effects of STX209 administration on MRS estimates of GABA and glutamate. The STX209 (30mg) intervention is the "high dose" | Drug | A. Placebo then 15mg then 30mg, B. 15mg then placebo then 30mg, C. 15mg then 30mg then placebo |
Primary outcome
M50 Latency (Left Hemisphere)
Time frame: 1 hour per intervention followed by a 1 week washout for a total of three weeks
The latency of the M50 auditory evoked response component arising from the left cerebral hemisphere
M50 Latency (Right Hemisphere)
Time frame: 1 hour per intervention followed by a 1 week washout for a total of three weeks
The latency of the M50 auditory evoked response component arising from the right cerebral hemisphere
Steady State Inter Trial Coherence (Left Hemisphere)
Time frame: 1 hour per intervention followed by a 1 week washout for a total of three weeks
The inter trial coherence (ITC) of auditory steady state response arising from the left cerebral hemisphere
Steady State Inter Trial Coherence (Right Hemisphere)
Time frame: 1 hour per intervention followed by a 1 week washout for a total of three weeks
The inter trial coherence (ITC) of auditory steady state response arising from the right cerebral hemisphere
GABA (Left Hemisphere)
Time frame: 1 hour per intervention followed by a 1 week washout for a total of three weeks
GABA/Cr ratio arising from a voxel in the left superior temporal gyrus
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Timothy Roberts, PhD principal investigator
Children's Hospital of Philadelphia
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 STX209 (15mg) and STX209 (30mg) in people with Autism Disorder, run by Timothy Roberts 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 9 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 21 Oct 2019. 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?
Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
M50 Latency (Left Hemisphere) (time frame: 1 hour per intervention followed by a 1 week washout for a total of three weeks). The study lists 5 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 21 Oct 2019.