Autism Spectrum DisorderPhase 3NCT01972074
Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
A Phase 3 study testing Memantine in people with Autism Spectrum Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study is a 12-week, randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment of social impairment in adolescents with autism spectrum disorder (ASD). Read more about this study
- Who is it for?
- Ages 8 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2015to 7 May 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- All Participants:
- Male and female participants, ages 8-17 years (inclusive)
- Participants with Autism Spectrum Disorder:
- Meets Diagnostic and Statistical Manual-5 autism spectrum disorder diagnostic criteria, as established by clinical diagnostic interview
- At least moderate severity of social impairment, as measured by a total raw score of ≥85 on the parent/guardian-completed Social Responsiveness Scale, Second Edition (SRS-2) and a score of ≥4 on the clinician-administered Autism Spectrum Disorder Clinical Global Impression-Severity scale (ASD CGI-S)
- Healthy Control Participants:
- 2. Age-, sex-, and IQ-matched with participants with autism spectrum disorder 3. No Axis I diagnoses, as established by the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E) and confirmed by clinical diagnostic interview 4. No significant traits of autism spectrum disorder, as measured by a total raw score of <60 on the parent/guardian-completed Social Responsiveness Scale, Second Edition
Who cannot join
- All Participants:
- IQ ≤70 based, on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) Vocabulary and Matrix Reasoning subtests
- Impaired communicative speech
- Current treatment with the following medications, which are known to impact glutamate levels:
- Lamotrigine
- Amantadine
Show all 23Show fewer
- N-acetylcysteine
- D-cycloserine
- Current treatment with a psychotropic medication, not listed above, on a dose that has not been stable for at least 4 weeks prior to study baseline
- Co-administration of drugs that compete with memantine for renal elimination using the same renal cationic system, including hydrochlorothiazide, triamterene, metformin, cimetidine, ranitidine, quinidine, and nicotine
- Initiation of a new psychosocial intervention within 30 days prior to randomization
- Participants who are pregnant and/or nursing
- Participants with a history of non-febrile seizures without a clear and resolved etiology
- Participants with a history of or a current liver or kidney disease
- Clinically unstable psychiatric conditions or judged to be at serious suicidal risk
- Participants who meet for alcohol or drug dependence or abuse on the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version. If the participant has a recent history of substance abuse, as an added precaution, there will be a 2-week washout period before initiating the trial. There are no known safety issues relating to memantine and recent history of substance abuse.
- Serious, stable or unstable, systemic illness, including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
- Participants with severe hepatic impairment (Liver Function Tests [LFTs] >3 times the Upper Limit of Normal [ULN])
- Participants with genitourinary conditions that raise urine Power of Hydrogen (pH) (e.g., renal tubular acidosis, severe infection of the urinary tract)
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
This study is a 12-week, randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment of social impairment in adolescents with autism spectrum disorder (ASD). The investigators will also conduct pre- and post-treatment neuroimaging (functional magnetic resonance imaging [fMRI] and hydrogen magnetic resonance spectroscopy [HMRS]) to assess neural functional deficits in adolescents with autism spectrum disorder compared to healthy volunteer adolescents. This pre- and post-neuroimaging will also be used to assess any effects of memantine therapy on neural function in adolescents with autism spectrum disorder. The investigators hypothesize that short-term memantine monotherapy will be safe, well-tolerated, and effective in improving the core symptoms of autism spectrum disorder in adolescents with autism spectrum disorder. Additionally, the investigators hypothesize that following memantine therapy, adolescents with autism spectrum disorder will exhibit a decrease in glutamate (Glu) concentration in the anterior cingulate cortex (ACC) and a change towards normalization in altered functional connectivity of the anterior cingulate cortex and medial temporal lobes, consistent with improvement in social impairments in autism spectrum disorder. The investigators hypothesize that compared to healthy volunteer participants, participants with autism spectrum disorder will significantly differ on neuroimaging measures at baseline but that following memantine therapy, the difference between autism spectrum disorder and healthy volunteer neuroimaging data will decrease.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Memantine, Placebo
- Keywords
- Autism spectrum disorder, Treatment, Adolescents, Memantine, functional Magnetic Resonance Imaging, MRS, Neuroimaging
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
Also called Namenda
Capsule
PlaceboOther
Capsule
| Study group | Role | What they receive |
|---|---|---|
| Memantine | Experimental | Participants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase.
Placebo: Capsule Receives: Drug: Memantine |
| Placebo | Placebo comparator | Participants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase.
Memantine: Capsule Receives: Other: Placebo |
| Control Group | No intervention | Healthy controls will undergo neuroimaging twice (12 weeks apart) and will receive no intervention during the 12-week window. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Responder
Treatment responders are defined as having a 25% reduction, from baseline to endpoint, in Social Responsiveness Scale, Second Edition: School-Age, Parent Report (SRS-2) total raw score and an Autism Spectrum Disorder Clinical Global Impression-Improvement (ASD CGI-I) score ≤2. The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item rating scale completed by the parents/guardians of children ages 4-18. It is used to measure the severity of autism spectrum disorder symptoms. Each item is rated on a 4-point Likert scale, ranging from 1=Not True to 4=Almost Always True. Higher scores indicate a higher severity of autism spectrum disorder symptoms. The Autism Spectrum Disorder Clinical Global Impression-Improvement subscale (ASD CGI-I) is a clinician-rated measure of the improvement of autism spectrum disorder symptoms. The subscale is rated on a 7-point Likert scale, ranging from 1=Very Much Improved to 7=Very Much Worse. Higher scores indicate less symptom improvement.
Measured: 12 Weeks (from Baseline [Week 0] to Endpoint [Week 12])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2013 (estimated)
- Study start17 Feb 2015
- Primary completion7 May 2018
- Study completion7 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Mclean Hospital
- Responsible party
- Principal investigator, Gagan Joshi, Massachusetts General Hospital
- Investigators
- Gagan Joshi, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01972074
- Sponsor's protocol ID
- 2013-P-001826
- Status last verified
- Jun 2024
- First submitted
- 24 Oct 2013
- Last updated
- 1 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Joshi G, Gonenc A, DiSalvo M, Faraone SV, Ceranoglu TA, Yule AM, Uchida M, McDougle CJ, Wozniak J. Memantine to Treat Social Impairment in Youths With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2025 Oct 1;8(10):e2534927. doi: 10.1001/jamanetworkopen.2025.34927.
PubMed 41032298Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013845. doi: 10.1002/14651858.CD013845.pub2.
PubMed 36006807
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT01972074
- Acronym / sponsor ID
- 2013-P-001826
- Conditions
- Autism Spectrum Disorder
- Keywords
- Autism spectrum disorder, Treatment, Adolescents, Memantine, functional Magnetic Resonance Imaging, MRS, Neuroimaging
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Mclean Hospital
- Study start
- 17 Feb 2015 (actual)
- Primary completion
- 7 May 2018 (actual)
- Study completion
- 7 May 2018 (actual)
- First posted
- 30 Oct 2013 (estimated)
- Results
- Posted 11 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a 12-week, randomized-controlled trial of memantine hydrochloride (Namenda) for the treatment of social impairment in adolescents with autism spectrum disorder (ASD). The investigators will also conduct pre- and post-treatment neuroimaging (functional magnetic resonance imaging [fMRI] and hydrogen magnetic resonance spectroscopy [HMRS]) to assess neural functional deficits in adolescents with autism spectrum disorder compared to healthy volunteer adolescents. This pre- and post-neuroimaging will also be used to assess any effects of memantine therapy on neural function in adolescents with autism spectrum disorder. The investigators hypothesize that short-term memantine monotherapy will be safe, well-tolerated, and effective in improving the core symptoms of autism spectrum disorder in adolescents with autism spectrum disorder. Additionally, the investigators hypothesize that following memantine therapy, adolescents with autism spectrum disorder will exhibit a decrease in glutamate (Glu) concentration in the anterior cingulate cortex (ACC) and a change towards normalization in altered functional connectivity of the anterior cingulate cortex and medial temporal lobes, consistent with improvement in social impairments in autism spectrum disorder. The investigators hypothesize that compared to healthy volunteer participants, participants with autism spectrum disorder will significantly differ on neuroimaging measures at baseline but that following memantine therapy, the difference between autism spectrum disorder and healthy volunteer neuroimaging data will decrease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Memantine | Experimental | Drug: MemantineParticipants in the placebo arm will receive placebo (no active ingredients) in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12-week treatment phase. Placebo: Capsule |
| Placebo | Placebo comparator | Other: PlaceboParticipants in the memantine arm will receive memantine in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4-week titration phase to a maximum dose of 20 mg per day). Participants will undergo neuroimaging before and after the 12-week treatment phase. Memantine: Capsule |
| Control Group | No intervention | –Healthy controls will undergo neuroimaging twice (12 weeks apart) and will receive no intervention during the 12-week window. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Male and female participants, ages 8-17 years (inclusive)
- Meets Diagnostic and Statistical Manual-5 autism spectrum disorder diagnostic criteria, as established by clinical diagnostic interview
- At least moderate severity of social impairment, as measured by a total raw score of ≥85 on the parent/guardian-completed Social Responsiveness Scale, Second Edition (SRS-2) and a score of ≥4 on the clinician-administered Autism Spectrum Disorder Clinical Global Impression-Severity scale (ASD CGI-S)
- 2. Age-, sex-, and IQ-matched with participants with autism spectrum disorder 3. No Axis I diagnoses, as established by the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E) and confirmed by clinical diagnostic interview 4. No significant traits of autism spectrum disorder, as measured by a total raw score of <60 on the parent/guardian-completed Social Responsiveness Scale, Second Edition
Key exclusion criteria (23 listed)
- IQ ≤70 based, on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) Vocabulary and Matrix Reasoning subtests
- Impaired communicative speech
- Current treatment with the following medications, which are known to impact glutamate levels:
- Current treatment with a psychotropic medication, not listed above, on a dose that has not been stable for at least 4 weeks prior to study baseline
- Co-administration of drugs that compete with memantine for renal elimination using the same renal cationic system, including hydrochlorothiazide, triamterene, metformin, cimetidine, ranitidine, quinidine, and nicotine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MemantineAlso: NamendaCapsule | Drug | Memantine |
| PlaceboCapsule | Other | Placebo |
Primary outcome
Treatment Responder
Time frame: 12 Weeks (from Baseline [Week 0] to Endpoint [Week 12])
Treatment responders are defined as having a 25% reduction, from baseline to endpoint, in Social Responsiveness Scale, Second Edition: School-Age, Parent Report (SRS-2) total raw score and an Autism Spectrum Disorder Clinical Global Impression-Improvement (ASD CGI-I) score ≤2. The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item rating scale completed by the parents/guardians of children ages 4-18. It is used to measure the severity of autism spectrum disorder symptoms. Each item is rated on a 4-point Likert scale, ranging from 1=Not True to 4=Almost Always True. Higher scores indicate a higher severity of autism spectrum disorder symptoms. The Autism Spectrum Disorder Clinical Global Impression-Improvement subscale (ASD CGI-I) is a clinician-rated measure of the improvement of autism spectrum disorder symptoms. The subscale is rated on a 7-point Likert scale, ranging from 1=Very Much Improved to 7=Very Much Worse. Higher scores indicate less symptom improvement.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41032298Joshi G, Gonenc A, DiSalvo M, Faraone SV, Ceranoglu TA, Yule AM, Uchida M, McDougle CJ, Wozniak J. Memantine to Treat Social Impairment in Youths With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2025 Oct 1;8(10):e2534927. doi: 10.1001/jamanetworkopen.2025.34927.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
- Derived from this study: PubMed 36006807Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013845. doi: 10.1002/14651858.CD013845.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gagan Joshi, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Memantine in people with Autism Spectrum Disorder, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Responder (time frame: 12 Weeks (from Baseline [Week 0] to Endpoint [Week 12])). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01972074, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024.