DAAOI-1 Treatment for Treatment-resistant Schizophrenia

China Medical University

Status and phase: Completed; Phase 2

Conditions: Schizophrenia

Treatments: Drug: DAAOI-1; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01390376

DOH99-TD-I-111-TM001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

60 participants in 3 patient groups, including a placebo group

BE 1

Experimental group

Description:

DAAOI-1 1g

Treatment:

Drug: DAAOI-1

Drug: DAAOI-1

BE 2

Experimental group

Description:

DAAOI-1 2g

Treatment:

Drug: DAAOI-1

Drug: DAAOI-1

starch pill

Placebo Comparator group

Treatment:

Drug: placebo