Predicting Treatment Response to Memantine in Autism Using Magnetic Resonance Spectroscopy

NCT02811627 | Completed Early Phase 1

• 1 other identifier: 2004983HS
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder

Keywords

Magnetic Resonance Spectroscopy; Memantine; Treatment prediction biomarker

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impressions - Improvement

  Clinician rated 7 item scale looking at improvements in specific aspects and overall level of autism

  12 weeks post start of memantine treatment

Secondary Outcomes (4)

• Social Responsiveness Scale (SRS)

  Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment

• General Social Outcomes Measure (GSOM)

  Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment

• Aberrant Behavior Checklist (ABC)

  Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment

• Test of Language Competence

  Baseline (before start of memantine treatment) and at 12 weeks post start of memantine treatment

Study Arms (1)

Memantine and Magnetic Resonance Imaging

EXPERIMENTAL

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; Device: Magnetic Resonance Imaging

Interventions

Memantine DRUG

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.

Also known as: Namenda

Memantine and Magnetic Resonance Imaging

Magnetic Resonance Imaging DEVICE

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.

Memantine and Magnetic Resonance Imaging

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Potential participants will be asked to take part in this study because he/she:
• has autism spectrum disorder
• is starting memantine off label for managing their autism symptoms
• is deemed safe to enter the MR environment using the attached screening form, and
• is capable of lying still for approximately 1.5 hour.

You may not qualify if:

• Subjects would be excluded if:
• 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,
• pregnancy
• claustrophobia
• memantine intolerance
• known hypersensitivity to memantine hydrochloride or
• inability to lie still for approximately 90 minutes.

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri

Columbia, Missouri, 65211, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Memantine; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• David Q Beversdorf, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Professor - Medicine: Radiology

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: June 23, 2016
• Study Start: June 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

US (1)