Clinical trial NCT01390376: DAAOI-1 Treatment for Treatment-resistant Schizophrenia
Official title: DAAOI-1 Treatment for Treatment-resistant Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
NMDA
DAAOI
Clozapine resistant schizophrenia
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: Department of Health, Executive Yuan, R.O.C. (Taiwan)
First posted: 2011-07-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue at present. According to the N-methyl-D-aspartate (NMDA) hypothesis, adjuvant NMDA-enhancing agents may have therapeutic benefit. DAAOI-1, a D-amino acid oxidase (DAAO) inhibitor, is a NMDA-enhancing agents.

The aim of this project is to examine the effectiveness and safety of DAAOI-1 adjuvant treatment for clozapine-resistant refractory schizophrenia patients in a randomized, double-blind, placebo - controlled trial.

Detailed description: Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue at present. Among schizophrenia patients, around 20-25%are treatment-resistant. According to the N-methyl-D-aspartate (NMDA) hypothesis, many clinical trials on NMDA-enhancing agents were studied. Adjuvant NMDA-enhancing agents, including glycine, D-amino acids (D-serine, D-alanine), and sarcosine (a glycine transporter I inhibitor), revealed beneficial but limited efficacy for positive and negative symptoms. The investigators recently started to study the potential of DAAOI-1, a D-amino acid oxidase (DAAO) inhibitor which can elevate synaptic concentration of D-amino acids.

The aims of this project is to examine the effectiveness and safety of DAAOI-1 adjuvant treatment for clozapine-resistant refractory schizophrenia patients in a randomized, double-blind, placebo - controlled trial.

Eligibility criteria: Inclusion Criteria:

* Fulfilled the DSM-IV criteria of schizophrenia
* Poor responder of clozapine: a 12-week treatment without satisfactory response: a minimal total score of 70 on the Positive and Negative Syndrome Scale (PANSS) (Kay 1987), and a minimal total score of 40 on the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen 1983).
* Agree to participate in the study and provide informed consent

Exclusion Criteria:

* Meet DSM-IV criteria of other AXIS I disorder, current substance dependence or mental retardation
* Serious medical or neurological illness
* Pregnancy or lactation
* Use of depot antipsychotic in the past 6 months
* Inability to follow protocol.

Primary outcomes:
measure: The severity of psychiatric symptoms
timeFrame: week 0, 2, 4, 6
Secondary outcomes:
measure: PANSS subscales
timeFrame: week 0,2,4,6
measure: Hamilton Depression Rating Scale (HAMD)
timeFrame: Week 0,2,4, 6
measure: Cognitive function
timeFrame: week 0, 6
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: