Clinical trial NCT02532686: DAAOI-2 add-on Treatment for Treatment-resistant Schizophrenia
Official title: DAAOI-2 add-on Treatment for Treatment-resistant Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Treatment resistant
DAAOI
NMDA
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, Taiwan
First posted: 2015-08-26
Enrollment: 40
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 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-2, a D-amino acid oxidase (DAAO) inhibitor, is a NMDA-enhancing agent. The aim of this project is to examine the effectiveness and safety of DAAOI-2 add-on treatment for treatment-resistant 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 is still a difficult clinical issue at present. 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 such as D-serine, and sarcosine (a glycine transporter I inhibitor), revealed beneficial but limited efficacy for positive and negative symptoms.

The aim of this project is to examine the effectiveness and safety of DAAOI-2 add-on treatment for treatment resistant schizophrenia patients in a randomized, double-blind, placebo - controlled trial.

Eligibility criteria: Inclusion Criteria:

* Fulfill the DSM-IV criteria of schizophrenia
* Treatment resistant: No satisfactory response to at least two kinds of antipsychotics
* Remain symptomatic but without clinically significant fluctuation and the antipsychotic doses are unchanged for at least 3 months
* Have a minimum baseline total score of 70 on the Positive and Negative Syndrome Scale (PANSS)
* Agree to participate in the study and provide informed consent

Exclusion Criteria:

* Meet DSM-IV criteria of substance (including alcohol) abuse or dependence
* Meet DSM-IV criteria of mental retardation
* Serious medical or neurological illness
* Pregnancy or lactation
* Inability to follow protocol

Primary outcomes:
measure: Positive and Negative Syndrome Scale(PANSS)
timeFrame: baseline
measure: Positive and Negative Syndrome Scale(PANSS)
timeFrame: 2 weeks after the trial
measure: Positive and Negative Syndrome Scale(PANSS)
timeFrame: 4 weeks after the trial
measure: Positive and Negative Syndrome Scale(PANSS)
timeFrame: 6 weeks after the trial (The end of the trial)
measure: Assessment of Negative symptoms(SANS)
timeFrame: baseline
measure: Assessment of Negative symptoms(SANS)
timeFrame: 2 weeks after the trial
measure: Assessment of Negative symptoms(SANS)
timeFrame: 4 weeks after the trial
measure: Assessment of Negative symptoms(SANS)
timeFrame: 6 weeks after the trial (The end of the trial)
Secondary outcomes:
measure: PANSS subscales
timeFrame: baseline
measure: PANSS subscales
timeFrame: 2 weeks after the trial
measure: PANSS subscales
timeFrame: 4 weeks after the trial
measure: PANSS subscales
timeFrame: 6 weeks after the trial (The end of the trial)
measure: Clinical Global Impression (CGI)
timeFrame: baseline
measure: Clinical Global Impression (CGI)
timeFrame: 2 weeks after the trial
measure: Clinical Global Impression (CGI)
timeFrame: 4 weeks after the trial
measure: Clinical Global Impression (CGI)
timeFrame: 6 weeks after the trial (The end of the trial)
measure: Global assessment of function (GAF)
timeFrame: baseline
measure: Global assessment of function (GAF)
timeFrame: 2 weeks after the trial
measure: Global assessment of function (GAF)
timeFrame: 4 weeks after the trial
measure: Global assessment of function (GAF)
timeFrame: 6 weeks after the trial (The end of the trial)
measure: Hamilton Depression Rating Scale (HAMD)
timeFrame: baseline
measure: Hamilton Depression Rating Scale (HAMD)
timeFrame: 2 weeks after the trial
measure: Hamilton Depression Rating Scale (HAMD)
timeFrame: 4 weeks after the trial
measure: Hamilton Depression Rating Scale (HAMD)
timeFrame: 6 weeks after the trial (The end of the trial)
measure: Quality of life scale (QOL)
timeFrame: baseline
measure: Quality of life scale (QOL)
timeFrame: 2 weeks after the trial
measure: Quality of life scale (QOL)
timeFrame: 4 weeks after the trial
measure: Quality of life scale (QOL)
timeFrame: 6 weeks after the trial (The end of the trial)
measure: "Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS]
timeFrame: baseline
measure: "Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS]
timeFrame: 6 weeks after the trial (The end of the trial)
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: