SchizophreniaNCT02233556
Effect of Memantine on ERP in Early Schizophrenia and Healthy Subjects
A study testing Memantine in people with Schizophrenia, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Patients with schizophrenia are deeply affected by the positive symptoms, negative symptoms and cognitive impairment. A generalized cognitive deficit could be frequently observed and traced back to early stage of the disease. Read more about this study
- Who is it for?
- Ages 20 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteTaiwan
- Study dates
- Feb 2014to Dec 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 20 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Both male and female outpatients
- Age 20-45 years old at the time of screening
- A diagnosis of schizophrenia based on the Structured Clinical Interview for DSM-IV
- A duration of illness for less than 5 years since initially diagnosed as schizophrenia
- Currently receiving treatment mainly by an atypical antipsychotic (risperidone, olanzapine, amisulpiride, aripiprazole, quetiapine, ziprasidone, paliperidone), including long-acting injectable antipsychotic
- A first generation antipsychotic agent only for a low-dose, as needed use purpose
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- No revised use of benzodiazepines, antidepressants, anticholinergics, or other concomitant medications during past 3 months
- Both male and female
- Age 20-45 years old at the time of screening
- No psychiatric diagnosis based on the Structured Clinical Interview for DSM-IV
- No current use of any pharmaceutical agents in past 2 weeks
Who cannot join
- A score of 5 or more on any of the 7 positive symptom items of the PANSS rating at screening
- Scores of 4 on at least 3 of the 7 positive symptom items of the PANSS rating at screening
- A major relapse resulting in readmission or doubling the dosage of previous effective antipsychotic treatment during the course of illness
- A change of current antipsychotic medication in recent 3 months
- Mental retardation known as IQ below 70 prior to the diagnosis of schizophrenia
- A history of pervasive mental disorder or bipolar disorder
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- A medical condition with significant cognitive sequelae
- A history of substance dependence
- A history of hypersensitivity to memantine or other drugs of the same class, such as amantadine
- Pregnancy, plan to get pregnant during the study period, or lactating women
- Abnormal liver function (AST, ALT higher than doubling the upper limits of normal range) or abnormal renal function (blood creatinine > 1.3 mg/dL)
- A history of epilepsy
- A history of myocardial infarction, congestive heart failure, uncontrolled hypertension, stroke, or severe heart block.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, Taiwan, 100
Ming-Hsien Hsieh, MD, PhD, +886-2-23123456 ext. 66790, mingh@ntuh.gov.tw
Cheng-Chung Liu, MD, PhD
About this study
Official title: Effects of Memantine on Event-related Potential in the Comparison of Patients With Early Schizophrenia and Healthy Subjects
Patients with schizophrenia are deeply affected by the positive symptoms, negative symptoms and cognitive impairment. A generalized cognitive deficit could be frequently observed and traced back to early stage of the disease. Currently medication intervention significantly improves positive symptoms through dopamine receptor modification, leaving alone the negative symptoms and cognitive impairment. Besides dopamine dysregulation, more and more attention had been paid to the association of N-methyl-D-aspartate (NMDA) type glutamate receptor and schizophrenia, focusing on the neurobiological and cognitive biomarkers change. Memantine, an uncompetitive antagonist of NMDA type glutamate receptor approved as cognitive enhancer for Alzheimer's disease, is a potential candidate for preventing cognitive decline of schizophrenia. Previous randomized clinical trials failed to demonstrate its efficacy on chronic schizophrenic patients and it might be related to the chronic and irreversible disease process. There is also study supporting that memantine induces change in mismatch negativity (MMN) in frontal cortex of healthy subjects. This study will compare the MMN change of healthy subjects and the population of early schizophrenia, who has persistent neurobiological, cognitive biomarkers or negative symptoms despite subsided positive symptoms. Both male and female aged 20-45 years old outpatients with a length of illness for less than 5 years since first diagnosed as schizophrenia, currently receiving treatment by atypical antipsychotics in a relatively stable condition will be recruited. Healthy subjects will be recruited comparing their age and sex. We plan to recruit 10 subjects for both patient and healthy subjects with a total of 20 participants. All participants will receive general clinical, cognitive and event-related potential (ERP) evaluation as baseline before taking medication. Twenty mg of memantine will be given 4 hours before ERP retest. The analyses will be performed based on the change of ERP using paired-t sample test. Baseline clinical and cognitive symptoms will be analyzed as possible confounders.
Read the detailed description
In this proposal, we use one-dose memantine trial to compare the difference of MMN change between healthy subjects and early schizophrenia patients. The cognitive and negative symptoms will be counted as possible confounding variables. We would like to make connection and association between neurobiological and neurocognitive markers for further treatment application.
The specific aim of this project is to test if memantine will influence the ERPs change, as in healthy subjects, in patients with early schizophrenia. The specific study population is been known of just have their first episode psychosis subsided, conventionally defined by significantly improved positive symptoms, yet some of them complaining of cognitive decline or presenting with persistent negative symptoms. Previous study showed improvement in mismatch negativity was correlated with general function improvement in schizophrenia. Although a recent study failed to demonstrate positive effects on residual psychopathology of a group of chronic stable schizophrenic patients. In this study we are targeting at a specific population of early schizophrenic patients to examine the efficacy of memantine on neurobiological markers and possible application to general psychopathology. Our objectives include:
- Test memantine effects on the change of ERPs, especially focus on mismatch negativity.
- Compare the ERP difference between healthy subjects and early schizophrenic patients
- Examine whether the effect of memantine will be affected by any significant baseline clinical variables or predisposed cognitive deficits.
First if we could replicate the ERP change in healthy subjects influenced by memantine, and we could further compare the difference between healthy subjects and patient subjects. It may support the hypothesis of NMDA-type glutamate receptor dysregulation theory in schizophrenia. If further association is detected through larger scale study between ERP and clinical symptoms, we could apply memantine in the add-on treatment of schizophrenia. As memantine is already an approved medicine for treatment of moderate to severe Alzheimer disease in many countries worldwide, hopefully we can add a new indication to its original clinical application. Thus it will become the first medicine that can help a condition which has rendered a lot of schizophrenic patients marked impairments in their social and occupational functioning from the early stage of their life. We believe this impact will be even bigger than the original indication of memantine, which is exclusively for patients with dementia. Rather than delaying deterioration of cognitive functioning in patient's late life, an adjuvant therapy for early intervention in schizophrenia aiming at improving cognitive function and hence restoring social and occupational functioning bears greater impact on a patient's life trajectory and lessen the burden of a society. Furthermore, the results from this project will provide critical evidence to support or refute the hypoglutaminergic theory of schizophrenia, which might be an important complement to the hyperdopaminergic theory. With a better understanding of the pathophysiology of schizophrenia not only focusing on dopaminergic system-related positive symptoms but also glutamatergic system-related cognitive and negative symptoms, will provide theoretic base of psychopharmacology in developing agents targeting at different systems to improve the outcome of schizophrenia from the early stage or even the putative pre-psychotic stage of the illness.
- Conditions
- Schizophrenia
- Being tested
- Memantine
- Keywords
- event-related potential, mismatch negativity, NMDA, Glutamate
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
Also called Ebixa 10 mg, manufactured by Lunbeck A/S, Denmark
Taking 20mg(2 capsules) of memantine, followed by Event related potential assessments as below:
- Mismatch negativity(MMN)
- P50
| Study group | Role | What they receive |
|---|---|---|
| Memantine | Experimental | This study has only one arm. i.e. Single dose of memantine 20mg Receives: Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in auditory event-related potentials "MMN"before/after intake of a single dose memantine
Previous studies revealed deficits in cognition via auditory event-related potential, such as Mismatch Negativity. This study would compare the effect of single dose memantine in MMN.
Measured: 4 hours after intake of a single dose memantine
Secondary outcomes (1)
Changes in auditory event-related potentials "P50" before/after intake of a single dose memantine
Previous studies revealed deficits in cognition via auditory event-related potential, such as P50. This study would compare the effect of single dose memantine in P50
Measured: 4 hours after intake of a single dose memantine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by National Taiwan University 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 N/A
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ming-Hsien Hsieh, MD, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02233556
- Sponsor's protocol ID
- 201308083MINB
- Status last verified
- Dec 2015
- First submitted
- 26 Feb 2014
- Last updated
- 14 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Memantine on Event-related Potential in the Comparison of Patients With Early Schizophrenia and Healthy Subjects
- ClinicalTrials.gov ID
- NCT02233556
- Acronym / sponsor ID
- 201308083MINB
- Conditions
- Schizophrenia
- Keywords
- event-related potential, mismatch negativity, NMDA, Glutamate
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 8 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with schizophrenia are deeply affected by the positive symptoms, negative symptoms and cognitive impairment. A generalized cognitive deficit could be frequently observed and traced back to early stage of the disease. Currently medication intervention significantly improves positive symptoms through dopamine receptor modification, leaving alone the negative symptoms and cognitive impairment. Besides dopamine dysregulation, more and more attention had been paid to the association of N-methyl-D-aspartate (NMDA) type glutamate receptor and schizophrenia, focusing on the neurobiological and cognitive biomarkers change. Memantine, an uncompetitive antagonist of NMDA type glutamate receptor approved as cognitive enhancer for Alzheimer's disease, is a potential candidate for preventing cognitive decline of schizophrenia. Previous randomized clinical trials failed to demonstrate its efficacy on chronic schizophrenic patients and it might be related to the chronic and irreversible disease process. There is also study supporting that memantine induces change in mismatch negativity (MMN) in frontal cortex of healthy subjects. This study will compare the MMN change of healthy subjects and the population of early schizophrenia, who has persistent neurobiological, cognitive biomarkers or negative symptoms despite subsided positive symptoms. Both male and female aged 20-45 years old outpatients with a length of illness for less than 5 years since first diagnosed as schizophrenia, currently receiving treatment by atypical antipsychotics in a relatively stable condition will be recruited. Healthy subjects will be recruited comparing their age and sex. We plan to recruit 10 subjects for both patient and healthy subjects with a total of 20 participants. All participants will receive general clinical, cognitive and event-related potential (ERP) evaluation as baseline before taking medication. Twenty mg of memantine will be given 4 hours before ERP retest. The analyses will be performed based on the change of ERP using paired-t sample test. Baseline clinical and cognitive symptoms will be analyzed as possible confounders.
Detailed description
In this proposal, we use one-dose memantine trial to compare the difference of MMN change between healthy subjects and early schizophrenia patients. The cognitive and negative symptoms will be counted as possible confounding variables. We would like to make connection and association between neurobiological and neurocognitive markers for further treatment application.
The specific aim of this project is to test if memantine will influence the ERPs change, as in healthy subjects, in patients with early schizophrenia. The specific study population is been known of just have their first episode psychosis subsided, conventionally defined by significantly improved positive symptoms, yet some of them complaining of cognitive decline or presenting with persistent negative symptoms. Previous study showed improvement in mismatch negativity was correlated with general function improvement in schizophrenia. Although a recent study failed to demonstrate positive effects on residual psychopathology of a group of chronic stable schizophrenic patients. In this study we are targeting at a specific population of early schizophrenic patients to examine the efficacy of memantine on neurobiological markers and possible application to general psychopathology. Our objectives include:
- Test memantine effects on the change of ERPs, especially focus on mismatch negativity.
- Compare the ERP difference between healthy subjects and early schizophrenic patients
- Examine whether the effect of memantine will be affected by any significant baseline clinical variables or predisposed cognitive deficits.
First if we could replicate the ERP change in healthy subjects influenced by memantine, and we could further compare the difference between healthy subjects and patient subjects. It may support the hypothesis of NMDA-type glutamate receptor dysregulation theory in schizophrenia. If further association is detected through larger scale study between ERP and clinical symptoms, we could apply memantine in the add-on treatment of schizophrenia. As memantine is already an approved medicine for treatment of moderate to severe Alzheimer disease in many countries worldwide, hopefully we can add a new indication to its original clinical application. Thus it will become the first medicine that can help a condition which has rendered a lot of schizophrenic patients marked impairments in their social and occupational functioning from the early stage of their life. We believe this impact will be even bigger than the original indication of memantine, which is exclusively for patients with dementia. Rather than delaying deterioration of cognitive functioning in patient's late life, an adjuvant therapy for early intervention in schizophrenia aiming at improving cognitive function and hence restoring social and occupational functioning bears greater impact on a patient's life trajectory and lessen the burden of a society. Furthermore, the results from this project will provide critical evidence to support or refute the hypoglutaminergic theory of schizophrenia, which might be an important complement to the hyperdopaminergic theory. With a better understanding of the pathophysiology of schizophrenia not only focusing on dopaminergic system-related positive symptoms but also glutamatergic system-related cognitive and negative symptoms, will provide theoretic base of psychopharmacology in developing agents targeting at different systems to improve the outcome of schizophrenia from the early stage or even the putative pre-psychotic stage of the illness.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Memantine | Experimental | Drug: MemantineThis study has only one arm. i.e. Single dose of memantine 20mg |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Both male and female outpatients
- Age 20-45 years old at the time of screening
- A diagnosis of schizophrenia based on the Structured Clinical Interview for DSM-IV
- A duration of illness for less than 5 years since initially diagnosed as schizophrenia
- Currently receiving treatment mainly by an atypical antipsychotic (risperidone, olanzapine, amisulpiride, aripiprazole, quetiapine, ziprasidone, paliperidone), including long-acting injectable antipsychotic
Key exclusion criteria (13 listed)
- A score of 5 or more on any of the 7 positive symptom items of the PANSS rating at screening
- Scores of 4 on at least 3 of the 7 positive symptom items of the PANSS rating at screening
- A major relapse resulting in readmission or doubling the dosage of previous effective antipsychotic treatment during the course of illness
- A change of current antipsychotic medication in recent 3 months
- Mental retardation known as IQ below 70 prior to the diagnosis of schizophrenia
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: Ebixa 10 mg, manufactured by Lunbeck A/S, DenmarkTaking 20mg(2 capsules) of memantine, followed by Event related potential assessments as below: 1. Mismatch negativity(MMN) 2. P50 | Drug | Memantine |
Primary outcome
Changes in auditory event-related potentials "MMN"before/after intake of a single dose memantine
Time frame: 4 hours after intake of a single dose memantine
Previous studies revealed deficits in cognition via auditory event-related potential, such as Mismatch Negativity. This study would compare the effect of single dose memantine in MMN.
1 secondary outcome
Changes in auditory event-related potentials "P50" before/after intake of a single dose memantine
Time frame: 4 hours after intake of a single dose memantine
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2015.
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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.
Ming-Hsien Hsieh, MD, PhD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Memantine in people with Schizophrenia, run by National Taiwan University Hospital at 1 site in Taiwan.
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 11 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 14 Dec 2015. 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 Taiwan. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ming-Hsien Hsieh, MD, PhD (+886-2-23123456 ext. 66790, mingh@ntuh.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in auditory event-related potentials "MMN"before/after intake of a single dose memantine (time frame: 4 hours after intake of a single dose memantine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Dec 2015.