MEG Study of Acute STX209 Effects in ASD

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Primary Purpose

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

STX209 (15mg)

placebo

STX209 (30mg)

About this trial

This is an interventional basic science trial for Autism Disorder focused on measuring dose titration study, electrophysiology

Eligibility Criteria

14 Years - 17 Years (Child)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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.

Sites / Locations

Children's Hospital of Phladelphia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

A. Placebo then 15mg then 30mg

B. 15mg then placebo then 30mg

C. 15mg then 30mg then placebo

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

M50 Latency (Left Hemisphere)

The latency of the M50 auditory evoked response component arising from the left cerebral hemisphere

M50 Latency (Right Hemisphere)

The latency of the M50 auditory evoked response component arising from the right cerebral hemisphere

Steady State Inter Trial Coherence (Left Hemisphere)

The inter trial coherence (ITC) of auditory steady state response arising from the left cerebral hemisphere

Steady State Inter Trial Coherence (Right Hemisphere)

The inter trial coherence (ITC) of auditory steady state response arising from the right cerebral hemisphere

GABA (Left Hemisphere)

GABA/Cr ratio arising from a voxel in the left superior temporal gyrus

Secondary Outcome Measures

Full Information

NCT ID

NCT02278328

First Posted

October 17, 2014

Last Updated

September 27, 2019

Sponsor

Timothy Roberts

Collaborators

Simons Foundation, Clinical Research Associates, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02278328

Brief Title

MEG Study of Acute STX209 Effects in ASD

Official Title

Magnetoencephalography / Magnetic Resonance Spectroscopy Dose Response Study of Arbaclofen in Autism Spectrum Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

February 2016 (undefined)

Primary Completion Date

July 30, 2018 (Actual)

Study Completion Date

September 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Timothy Roberts

Collaborators

Simons Foundation, Clinical Research Associates, LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Disorder

Keywords

dose titration study, electrophysiology

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

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)

Masking Description

Each participant receives dose of drug or placebo. Both participant and investigator are masked to dose level/placebo. It is not open label.

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A. Placebo then 15mg then 30mg

Arm Type

Experimental

Arm Description

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.

Arm Title

B. 15mg then placebo then 30mg

Arm Type

Experimental

Arm Description

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.

Arm Title

C. 15mg then 30mg then placebo

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

STX209 (15mg)

Other Intervention Name(s)

Arbaclofen (15mg)

Intervention Description

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"

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

STX209 (30mg)

Other Intervention Name(s)

Arbaclofen (30mg)

Intervention Description

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"

Primary Outcome Measure Information:

Title

M50 Latency (Left Hemisphere)

Description

The latency of the M50 auditory evoked response component arising from the left cerebral hemisphere

Time Frame