Autism Spectrum Disorders
Conditions
Keywords
Memantine, Namenda, Autism Spectrum Disorders, Pervasive Developmental Disorders, Adults
Brief summary
The main objective of this study is to evaluate the safety and effectiveness of memantine (Namenda®) for cognitive and behavioral impairment in adults ages 18-50 years with autism spectrum disorders (ASD). This is an exploratory, 12-week, pilot study, seeking to determine whether Namenda is efficacious and well tolerated in the treatment of adults with ASD. The study results will be used to generate hypotheses for a larger randomized controlled clinical trial with explicit hypotheses and sufficient statistical power.
Interventions
DRUGMemantine
Memantine (Namenda®) was approved by the U.S. Food and Drug Administration in 2003 and by the European Agency for the Evaluation of Medical Products in 2002 for the treatment of moderate to severe Alzheimer's disease. Evidence from available treatment trials of memantine in ASD and non-ASD populations of youth and adults strongly suggest that memantine could be an effective agent for the treatment of adults with ASD. During the 12 weeks of study duration, subjects will be evaluated at weekly intervals for the first 4 weeks and thereafter every 3 weeks. Memantine will be administered in divided dose twice a day in the morning and evening. Titration of study medication will be guided by a forced titration schedule with an option for slower titration or holding at lower dose per clinician judgment. Safety, effectiveness, response and side effects will be evaluated.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Inclusions * Male and female outpatients 18-50 years of age. * Participants must have DSM-IV-TR diagnosis of PDD and displaying PDD symptoms with at least moderate impairment (SRS score ≥ 85 and CGI-PDD ≥ 4). * Fulfills diagnosis of autism spectrum disorders by meeting DSM-IV-TR PDD diagnostic criteria of autistic disorder (with the exception of a total lack of spoken language), Asperger's disorder, or PDD-NOS as established by clinical interview and confirmed by DICA-R PDD module. * Subjects and/or their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. * Subjects and/or their legal representative must be considered reliable reporters. * Each subject and/or their authorized legal representative must understand the nature of the study. The subject and/or their legal representative must sign an informed consent document. * Subject must be able to participate in mandatory blood draws. * Subject must be able to swallow pills. * Subjects with mood, anxiety, or disruptive behavior disorders will be allowed to participate in the study provided they do not meet any exclusionary criteria. Exclusions * IQ \< 85. * Total lack of spoken language. * DSM-IV-TR PDD diagnoses of Rett's disorder, or childhood disintegrative disorder. * Clinically unstable psychiatric conditions or judged to be at serious suicidal risk. * Active symptoms of anorexia or bulimia nervosa * Current diagnosis of a psychotic disorder or unstable bipolar disorder. * History of recent or current (past 30 days) clinically significant depressive or anxiety disorder that warrants treatment. * Current diagnosis of schizophrenia. * History of substance use (except nicotine or caffeine) within past 3 months * Serious, stable or unstable systemic illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. * Subjects with severe hepatic impairment (LFTs \> 3 times ULN) and those with severely impaired renal function (eGFR \< 30). * Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract). * Uncorrected hypothyroidism or hyperthyroidism. * Subjects with untreated and/or unstable diabetes. * Non-febrile seizures without a clear and resolved etiology. * Pregnant or nursing females. * Known hypersensitivity to memantine. * Severe allergies or multiple adverse drug reactions. * A non-responder or history of intolerance to memantine, after treatment at adequate doses as determined by the clinician. * Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction in ASD Symptom Severity as Defined by the Social Responsiveness Scale (SRS) | Week 12 | Number of participants with reduction in ASD symptom severity defined as a reduction in Social Responsiveness Scale (SRS) score from baseline of greater than or equal to 30%. The SRS is a 65-item rating scale completed by an informant to measure the severity of autism spectrum symptoms as they occur in natural settings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction in ASD Symptom Severity as Defined by the NIMH Clinical Global Impression for Pervasive Developmental Disorders (CGI-PDD) Improvement Score | Pre-treatment - 12 weeks | Number of participants with reduction in ASD symptom severity defined as an NIMH Clinical Global Impression (CGI) Pervasive Developmental Disorder (PDD) Improvement score less than or equal to 2. The CGI-Improvement is a clinician-rated measure of improvement. Scores range from 1 (very much improved) to 7 (very much worse) for PDD. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by local print and Internet advertising. Participants were also recruited from the referral pool of patients in the Pediatric Psychopharmacology Program at the MGH and from the Alan and Lorraine Bressler Clinic and Research Program for ASDs.
Participants by arm
| Arm | Count |
|---|---|
| Memantine (Namenda) Treatment Memantine (Namenda®) was approved by the U.S. Food and Drug Administration in 2003 and by the European Agency for the Evaluation of Medical Products in 2002 for the treatment of moderate to severe Alzheimer's disease. Evidence from available treatment trials of memantine in ASD and non-ASD populations of youth and adults strongly suggest that memantine could be an effective agent for the treatment of adults with ASD.
During the 12 weeks of study duration, subjects were evaluated at weekly intervals for the first 4 weeks and thereafter every 3 weeks. Memantine was administered in divided dose twice a day in the morning and evening. Titration of study medication was guided by a forced titration schedule with an option for slower titration or holding at lower dose per clinician judgment. Safety, effectiveness, response and side effects were evaluated. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Memantine (Namenda) Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 28.0 Years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Number of Participants With Reduction in ASD Symptom Severity as Defined by the Social Responsiveness Scale (SRS)
Number of participants with reduction in ASD symptom severity defined as a reduction in Social Responsiveness Scale (SRS) score from baseline of greater than or equal to 30%. The SRS is a 65-item rating scale completed by an informant to measure the severity of autism spectrum symptoms as they occur in natural settings.
Time frame: Week 12
Population: 19 participants were exposed to the medication, but 1 withdrew due to feeling mildly sedated which affected his driving. This occurred too early in the study for him to be analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Memantine (Namenda) Treatment | Number of Participants With Reduction in ASD Symptom Severity as Defined by the Social Responsiveness Scale (SRS) | 6 participants |
Secondary
Number of Participants With Reduction in ASD Symptom Severity as Defined by the NIMH Clinical Global Impression for Pervasive Developmental Disorders (CGI-PDD) Improvement Score
Number of participants with reduction in ASD symptom severity defined as an NIMH Clinical Global Impression (CGI) Pervasive Developmental Disorder (PDD) Improvement score less than or equal to 2. The CGI-Improvement is a clinician-rated measure of improvement. Scores range from 1 (very much improved) to 7 (very much worse) for PDD.
Time frame: Pre-treatment - 12 weeks
Population: 19 participants were exposed to the medication, but 1 withdrew due to feeling mildly sedated which affected his driving. This occurred too early in the study for him to be analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Memantine (Namenda) Treatment | Number of Participants With Reduction in ASD Symptom Severity as Defined by the NIMH Clinical Global Impression for Pervasive Developmental Disorders (CGI-PDD) Improvement Score | 15 participants |