MEG Study of Acute STX209 Effects in ASD

NCT02278328 | Completed Early Phase 1 Results DMC

• 1 other identifier: 14-010857
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Disorder

Keywords

dose titration study; electrophysiology

Outcome Measures

Primary Outcomes (5)

• M50 Latency (Left Hemisphere)

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

  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

  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

  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

  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

  1 hour per intervention followed by a 1 week washout for a total of three weeks

Study Arms (3)

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.

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.

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.

Drug: STX209 (15mg); Drug: placebo; Drug: STX209 (30mg)

Interventions

STX209 (15mg) DRUG

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"

Also known as: Arbaclofen (15mg)

A. Placebo then 15mg then 30mg; B. 15mg then placebo then 30mg; C. 15mg then 30mg then placebo

placebo DRUG

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

A. Placebo then 15mg then 30mg; B. 15mg then placebo then 30mg; C. 15mg then 30mg then placebo

STX209 (30mg) DRUG

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"

Also known as: Arbaclofen (30mg)

A. Placebo then 15mg then 30mg; B. 15mg then placebo then 30mg; C. 15mg then 30mg then placebo

Eligibility Criteria

• Age: 14 Years - 17 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Timothy Roberts: lead
• Simons Foundation: collaborator
• Clinical Research Associates, LLC: collaborator

Study Sites (1)

Children's Hospital of Phladelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Autistic Disorder

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Timothy Roberts, Professor
• Organization: Children's Hospital of Philadelphia

robertstim@email.chop.edu

267 426 0307

Study Officials

• Timothy Roberts, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Each participant receives dose of drug or placebo. Both participant and investigator are masked to dose level/placebo. It is not open label.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Oberkircher Family Chair in Pediatric Radiology Vice-Chair Radiology Research Children's Hospital of Philadelphia

Model Details: 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.

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 30, 2014
• Study Start: February 1, 2016
• Primary Completion: July 30, 2018
• Study Completion: September 27, 2019
• Last Updated: October 21, 2019
• Results First Posted: October 21, 2019

Record last verified: 2019-09

Locations

US (1)