A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)

Autism Spectrum Disorder Clinical Trial

Official title:

A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism Targeting Memory and Motor Planning

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01372449
• Other study ID #: 111576
• Status: Completed
• Phase: Phase 2
• First received: June 2, 2011
• Last updated: March 17, 2017
• Start date: December 2011
• Est. completion date: October 2015

Study information

• Verified date: March 2017
• Source: Anagnostou, Evdokia, M.D.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will attempt to study the effect of memantine, on memory, and motor praxis/expressive language skills in children with autism.

The investigators will recruit children ages 6-12 years who are verbal and meet criteria for Autism Spectrum Disorder. The children will be assessed for memory function, expressive language output and motor skills/praxis. They will then be randomized to memantine or placebo for 6 months. The effects of this medication and its safety in this population will be studied over the 6 month period.

Description:

Abnormalities in the modulation of the glutamate system have been reported by multiple investigators studying animal models, post-mortem brains, and single gene disorders that have overlapping phenotypes with autism. Abnormalities in glutamatergic function have been reported in disorders affecting a variety of behavioral and neurological domains, from mood stability, to cognitive flexibility, memory, and motor function. Numerous studies have reported a variety of memory and motor deficits in children with autism. Whereas the neurobiology of such deficits is an area of active research, there is a paucity of intervention research for such deficits in autism. This study will attempt to study the effect of an N-methyl-D-aspartate receptor (NMDA) inhibitor, memantine, on memory, and motor praxis/expressive language skills in children with autism.

Methods: Children ages 6-12 years who are verbal and meet criteria for Autism Spectrum Disorder will be recruited across 2 sites. After consent, the children will be assessed for memory function, expressive language output and motor skills/praxis. They will then be randomized 1:1 to memantine versus placebo for 6 months. The effects of this medication on the above mentioned symptoms domains as well as its safety in this population will be studied over the 6 month period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria

1. Male or female outpatients 6 to 12 years of age

2. Verbal; Module 2 or 3 on Autism Diagnostic Observation Schedule (ADOS)

3. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) for Autism Spectrum Disorder. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised (ADI-R) and ADOS Module 2 or 3.

4. Parents report difficulties with motor skills

5. Have a Clinician's Global Impression-Severity (CGI-S) score = 4 (moderately ill) at Screening and Baseline

6. If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study

7. Participants can be on up to 2 concomitant psychotropic medications before entering the study, provided that they have been on a stable dose for 30 days and have no plans to adjust the dose for the duration of study

8. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators

9. Prior to the conduct of any study-specific procedures, the patient must provide assent to participate in the study (if developmentally appropriate), and the parent or legal guardian must provide written informed consent

10. The patient and the patient's parent or legal guardian must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments

11. The parent or legal guardian must be capable of providing reliable information about the patient's condition, agree to oversee the administration of study drug, and accompany the patient to all clinic visits

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age

2. Patients with any primary psychiatric diagnosis other than autism at Screening: a history of Attention Deficit Hyperactivity Disorder (ADHD), bipolar disorder, psychosis, post-traumatic stress disorder, schizophrenia, or major depressive disorder

3. Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal MRI/structural lesion of the brain

4. Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.

5. Patients who plan to initiate or change pharmacological or nonpharmacologic interventions during the course of the study

6. Patients on d-cycloserine or riluzole as they both target the glutamate system

7. Patients on agents that alkalinize the urine (acetazolamide, potassium citrate, and sodium bicarbonate), as they decrease the elimination of memantine

8. Patients who have received treatment with memantine in the past with no response

9. Patients with a history of hypersensitivity reaction to dextromethorphan, amantadine, or any other NMDA receptor antagonists

10. Patients unable to tolerate venipuncture procedures for blood sampling

11. Patients who, in the Investigator's opinion, might not be suitable for the study

12. Children weighing under 20 kg (to meet FDA approvals)

13. Patients with a positive pregnancy test

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder

Intervention

Drug:
• Memantine
Memantine will be initiated at 3 mg. The dose will be increased every week by 3 mg for a maximum of 12mg for subjects weighing = 60kg, 9mg for subjects weighing = 40 kg but <60 kg, and 6 mg for subjects weighing = 20 kg but < 40kg.
• Placebo

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Evdokia Anagnostou	Icahn School of Medicine at Mount Sinai, Nationwide Children's Hospital, Rush University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Developmental Neuropsychological Assessment (NEPSY) Apraxia and Repetition of Nonsense Words Subtests	Outcome Measure is going to report a change. The NEPSY provides a developmental neuropsychological assessment for children age 3-12. It was designed to assess basic and complex aspects of cognitive capacities that are critical to children's ability to learn and be productive both in and out of school settings	Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial)
Primary	Expressive Vocabulary Test (EVT)		Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial)
Secondary	Vineland Adaptive Behavior Scale - Revised	Outcome Measure is going to report a change. The Vineland Scale is a semi-structured informant interview that assesses subjects' daily functioning. It is typically administered to a caretaker/family member. This scale has been found to assess social deficits in autism and relative strengths in daily living skills.	Baseline, Week 12, Week 24 (Measuring change from Baseline, middle of trial and end of trial)
Secondary	Safety Monitoring Uniform Research Form	The SMURF consists of three parts. Part 1 contains a "General Inquiry" to obtain all information about possible physical complaints, using general probes. Part 2 comprises "Specific Inquiries" about physical complaints, organized roughly around different body systems. Part 3 concludes with a "Closing Inquiry" in which the clinician can ask about any physical or other problems he/she has pre-existing knowledge about or which he/she noticed during the rest of the inquiry.	Screening, Baseline, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 16, Week 20, Week 24