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MEG Study of Acute STX209 Effects in ASD

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ClinicalTrials.gov Identifier: NCT02278328
Recruitment Status : Completed
First Posted : October 30, 2014
Results First Posted : October 21, 2019
Last Update Posted : October 21, 2019
Sponsor:
Collaborators:
Simons Foundation
Clinical Research Associates, LLC
Information provided by (Responsible Party):
Timothy Roberts, Children's Hospital of Philadelphia

Tracking Information
First Submitted Date  ICMJE October 17, 2014
First Posted Date  ICMJE October 30, 2014
Results First Submitted Date  ICMJE June 19, 2019
Results First Posted Date  ICMJE October 21, 2019
Last Update Posted Date October 21, 2019
Study Start Date  ICMJE February 2016
Actual Primary Completion Date July 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2019)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: October 29, 2014)
Responsiveness (sensitivity to change) of MEG measures to acute administration of STX209 at 3 dose levels. [ Time Frame: Participants will be followed over 5 visits, for an expected average of 5 weeks ]
To determine whether STX209 produces a significant change in MEG target parameters compared to baseline as well as compared to placebo treatment.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MEG Study of Acute STX209 Effects in ASD
Official Title  ICMJE Magnetoencephalography / Magnetic Resonance Spectroscopy Dose Response Study of Arbaclofen in Autism Spectrum Disorder
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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.
Primary Purpose: Basic Science
Condition  ICMJE Autism Disorder
Intervention  ICMJE
  • Drug: STX209 (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"
    Other Name: Arbaclofen (15mg)
  • Drug: placebo
    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
  • Drug: STX209 (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"
    Other Name: Arbaclofen (30mg)
Study Arms  ICMJE
  • Experimental: A. Placebo then 15mg then 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.

    Interventions:
    • Drug: STX209 (15mg)
    • Drug: placebo
    • Drug: STX209 (30mg)
  • Experimental: B. 15mg then placebo then 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.

    Interventions:
    • Drug: STX209 (15mg)
    • Drug: placebo
    • Drug: STX209 (30mg)
  • Experimental: C. 15mg then 30mg then placebo

    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.

    Interventions:
    • Drug: STX209 (15mg)
    • Drug: placebo
    • Drug: STX209 (30mg)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2019)
25
Original Estimated Enrollment  ICMJE
 (submitted: October 29, 2014)
8
Actual Study Completion Date  ICMJE September 27, 2019
Actual Primary Completion Date July 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Right- handed males aged 14 to 17.75 years.
  2. 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.
  3. Current pharmacological treatment regimen has been stable for at least 4 weeks prior to Screening.
  4. 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.
  5. 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:

  1. No known neurological impairment (e.g., head trauma with loss of consciousness for more than 10 minutes, stroke, seizure disorder).
  2. Claustrophobia
  3. Metallic implanted prosthetic or stimulation device (including pacemaker)
  4. Excessive metallic dental work (including braces, non-removable retainers)
  5. Subjects who are currently receiving treatment with racemic baclofen, vigabatrin, tiagabine, or riluzole.
  6. Subjects who have taken another investigational drug within the last 30 days.
  7. Subjects who are not able to take oral medications.
  8. Subjects who have a history of hypersensitivity to racemic baclofen.
  9. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 14 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02278328
Other Study ID Numbers  ICMJE 14-010857
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Timothy Roberts, Children's Hospital of Philadelphia
Study Sponsor  ICMJE Timothy Roberts
Collaborators  ICMJE
  • Simons Foundation
  • Clinical Research Associates, LLC
Investigators  ICMJE
Principal Investigator: Timothy Roberts, PhD Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP