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Predicting Treatment Response to Memantine in Autism Using Magnetic Resonance Spectroscopy

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ClinicalTrials.gov Identifier: NCT02811627
Recruitment Status : Recruiting
First Posted : June 23, 2016
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
David Beversdorf, University of Missouri-Columbia

Brief Summary:

Memantine, an N-methyl-D-aspartate receptor antagonist, has been explored as a possible therapeutic agent that reduces the excitatory (glutamate) - inhibitory (gamma amino-butyric acid, GABA) imbalance in autism pathology and improves social and communication deficits. While some studies have shown positive results, a large clinical trial failed to show benefit possibly because different subsets of autism responded differently to the treatment.

The investigator proposes a pilot, exploratory, clinical follow-on study using proton magnetic resonance spectroscopy (1H-MRS) to determine whether baseline glutamate/GABA levels in certain regions of the brain may help predict treatment response to Memantine in autistic subjects. At study onset, subjects will be assessed on the behavioral scales such as the Aberrant Behavior Checklist and Clinical Global Impressions scale, followed by MRS imaging. Memantine treatment will be started post imaging. Assessment measures will be repeated at week 12 during treatment. Glutamate and GABA levels in brain regions will be correlated to improvements on assessment measures. Expected results include higher glutamate and/or lower GABA levels in the anterior cingulate cortex at baseline in responders to memantine. If the hypotheses are confirmed, it will provide evidence of a relevant neural biomarker to predict treatment response to memantine with important implications for clinical care including improving individualization of treatments.


Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Drug: Memantine Device: Magnetic Resonance Imaging Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Predicting Treatment Response to Memantine in Autism Spectrum Disorder Using MR Spectroscopy
Study Start Date : June 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Memantine and Magnetic Resonance Imaging

Subjects will be started on memantine post the imaging session.

Memantine is available commercially as Namenda, Namenda XR and in the liquid form (for subjects who do not wish to take pills). Namenda (pill and the liquid) will be started at 5 mg/day doses to be titrated up 20 mg/day based on response and tolerability, as per the package insert instructions and based upon clinical titration in other clinical trials for a period of 12 weeks. Namenda XR will be started at 7 mg/day to be titrated up to 28mg/day based on response and tolerability, as per package insert instructions and based upon clinical titration in other clinical trials for a period of 12 weeks.

Drug: Memantine
Namenda (pill and the liquid) will be started at 5 mg/day doses to be titrated up 20 mg/day based on response and tolerability, as per the package insert instructions and based upon clinical titration in other clinical trials for a period of 12 weeks. Namenda XR will be started at 7 mg/day to be titrated up to 28mg/day based on response and tolerability, as per package insert instructions and based upon clinical titration in other clinical trials for a period of 12 weeks.
Other Name: Namenda

Device: Magnetic Resonance Imaging
The subjects will undergo an MRI assessment after baseline behavioral assessment. The session will involve a structural MRI scan, single voxel spectroscopy scans and resting state functional MRI. The subjects will be started on memantine post the imaging session. The imaging will be carried out on a research dedicated 3 Tesla (3T) Siemens Trio Scanner at the University of Missouri Brain Imaging Center by trained personnel.




Primary Outcome Measures :
  1. Clinical Global Impressions - Improvement [ Time Frame: 12 weeks post start of memantine treatment ]
    Clinician rated 7 item scale looking at improvements in specific aspects and overall level of autism


Secondary Outcome Measures :
  1. Social Responsiveness Scale (SRS) [ Time Frame: Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment ]
    Assessment of baseline social deficits before treatment onset and improvement in social functioning 12 weeks after starting memantine treatment. The Social Responsiveness Scale (SRS) is a 65 item questionnaire rated on a 4 point Likert scale to evaluate social impairments in autism. Higher scores on the SRS indicate severe impairments in social skills while lower scores indicate mild to moderate impairment in social skills. Total raw score pre and post treatment will be compared.

  2. General Social Outcomes Measure (GSOM) [ Time Frame: Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment ]
    The General Social Outcomes Measure assesses individuals with autism on five sub scales including Conversational Reciprocity, Social Problem solving, Affect Demonstration and Emotional Perspective Taking. Assessment of baseline social deficits before treatment onset and improvement in social functioning 12 weeks after starting memantine treatment. Lower scores indicate more severe impairment of social deficits while higher scores indicate improvements in social functioning. Scores on individual sub scales pre and post treatment will be compared.

  3. Aberrant Behavior Checklist (ABC) [ Time Frame: Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment ]
    Assessment of baseline and post-treatment levels of irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity or noncompliance and inappropriate speech. Higher scores indicate greater impairments.

  4. Test of Language Competence [ Time Frame: Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment ]
    Assesses language comprehension and verbal skills. Includes multiple sub tests such as Ambiguous Sentences, Figurative Speech and Recreating Oral Expressions. Higher scores indicate low levels of impairment in the domain. Scores on the individual sub scales will be compared pre and post treatment to assess improvements.



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Potential participants will be asked to take part in this study because he/she:

    1. has autism spectrum disorder
    2. is starting memantine off label for managing their autism symptoms
    3. is deemed safe to enter the MR environment using the attached screening form, and
    4. is capable of lying still for approximately 1.5 hour.

Exclusion Criteria:

  • Subjects would be excluded if:

    1. they have certain types of metallic implants, risk of exposure to metallic foreign bodies, pacemakers, magnetically sensitive implants that cannot be removed or are not securely attached,
    2. pregnancy
    3. claustrophobia
    4. memantine intolerance
    5. known hypersensitivity to memantine hydrochloride or
    6. inability to lie still for approximately 90 minutes.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02811627


Contacts
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Contact: David Q Beversdorf, MD 573-884-1871 beversdorfd@health.missouri.edu

Locations
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United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65211
Contact: David Q Beversdorf, MD    573-884-1871    beversdorfd@health.missouri.edu   
Sponsors and Collaborators
University of Missouri-Columbia
Investigators
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Principal Investigator: David Q Beversdorf, MD University of Missouri-Columbia
  Study Documents (Full-Text)

Documents provided by David Beversdorf, University of Missouri-Columbia:
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Responsible Party: David Beversdorf, Assoc. Professor - Medicine: Radiology, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT02811627    
Other Study ID Numbers: 2004983HS
First Posted: June 23, 2016    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: March 2020
Keywords provided by David Beversdorf, University of Missouri-Columbia:
Magnetic Resonance Spectroscopy
Memantine
Treatment prediction biomarker
Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents