Trial for Antidepressant Treatment for Negative Symptom of Schizophrenia With NRG1 Risk Genotype (TANESN)

March 9, 2010 updated by: National Taiwan University Hospital

A Double-blind, Randomized, Placebo Controlled Clinical Trial on Comparing Escitalopram and Duloxetine add-on for Negative Symptoms in Schizophrenic Subjects With Neuregulin-1 (NRG1) Risk Genotype

The project is a double-blind, randomized, placebo controlled clinical trial comparing 3 groups of schizophrenic subjects, who have no less than moderate degree of negative symptoms and carry the homozygous risk genotype (TT) of NRG1-P3, each group having 30 individuals, treated by add-on with escitalopram 10-20 mg/day, duloxetine 30-60 mg/day, and placebo. The treatment duration is 8 week. The investigators will evaluate the Positive and Negative Symptom Scale (PANSS) at baseline, Day 14, Day 28, Day 42, and Day 56. The primary outcome of interest will be the differences of averaged reduction of negative symptom scores among 3 groups and an average decrease of 2 or more in the negative symptoms will be indicated as improvement.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Negative symptoms of schizophrenia are enduring and detrimental. The underlying pathophysiology of negative symptoms is yet to be understood. Previous clinical trials of antidepressants as add-on therapy for negative symptoms in schizophrenia patients usually found merely a trend favoring augmentation strategy. Since schizophrenia is a heterogeneous disorder, clinical studies are often unable to reveal conclusive results. Thus efforts have been made to classify relatively homogeneous groups of patients by different approaches. Here, we proposed a translational study originating from our novel results of animal study and genetic study describe as the follows.We studied the neurobiological difference of the mice with the heterozygous deletion of NRG1(NRG1+/-mice)in comparison with their wild-type littermates. It was found that the antidepressant effect of desipramine for the immobilization was markedly increased in NRG1+/-mice assessed by two models, forced swimming test and tail suspension test. Furthermore, the expression of serotonin transporter (SERT) was up-regulated in most brain regions in NRG1+/-mice, indicating that the basal activity of serotonin was reduced because of higher uptake rate in NRG1+/-mice. Our data indicate that serotonin hypo-function may be involved in the immobilization symptom of schizophrenia with NRG1 defect. Increased immobility of forced swimming test in mice was suggested to be an animal model of negative symptoms. Thus our study implied that serotonin transporter blockers may be beneficial for the treatment of negative symptoms in some subtypes of schizophrenia, especially for the patients with NRG1 defect, which could be tested by examining specific polymorphism of NRG1 gene.We have identified a novel promoter variant (TC), named NRG1-P3, located on the promoter region of type V NRG1, from a direct sequencing study in Taiwanese schizophrenic patients and found it was significantly associated with schizophrenia in a large case-control sample. Through the luciferase reporter assay, we found the promoter construct with the risk genetic variant (T allele) of NRG1-P3 has significant lower luciferase reporter activity than that with the protected allele (C allele). It implied the schizophrenic patients with the T allele of NRG1-P3 might have lower NRG1 expression than those with the C allele. It is hypothesized that the negative symptoms of the schizophrenic patients with the T allele of NRG1-P3 will be more responsive to the SSRI or SNRI treatment.The project is a double-blind, randomized, placebo controlled clinical trial comparing 3 groups of schizophrenic subjects, who have no less than moderate degree of negative symptoms and carry the homozygous risk genotype (TT) of NRG1-P3, each group having 30 individuals, treated by add-on with escitalopram 10-20 mg/day, duloxetine 30-60 mg/day, and placebo. The treatment duration is 8 week. We will evaluate the Positive and Negative Symptom Scale (PANSS) at baseline, Day 14, Day 28, Day 42, and Day 56. The primary outcome of interest will be the differences of averaged reduction of negative symptom scores among 3 groups and an average decrease of 2 or more in the negative symptoms will be indicated as improvement.The project is novel and feasible because (1) it is the first clinical trial for the treatment of negative symptoms according to different genotypes of the patients and helps fulfill the prospect of individualized medication. (2) the research findings the translational study based upon are novel and unique and comes from our research team. (3) our research team mastered in clinical studies and has many clinical resources to recruit enough patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. aged between 18-65
  2. meet the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) schizophrenia
  3. the genotype of NRG1-P3 is the homozygous risk genotype (TT)
  4. under second-generation antipsychotic treatment with relatively stable clinical status (no change of prescribed medications during past 8 weeks and all symptom items in the positive subscale of PANSS with score no more than 4)
  5. having moderate to marked negative symptoms (scores between 4 to 6 in the items of N2, emotional withdrawal, and N4, passivity/apathetic social withdrawal)

Exclusion Criteria:

  1. lifetime diagnosis of schizoaffective disorder, bipolar affective disorder, and major depressive disorder and the score of Hamilton Depression Rating Scale (HAM-D) is above 18
  2. the genotype of NRG1-P3 is TC or CC
  3. having any major systemic illness
  4. receiving first-generation antipsychotics or already on antidepressants or mood-stabilizing agents adjuvant
  5. substance abuse in the past 6 months
  6. pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A
Drug: Lexapro
10mg/cap 1~2# QD
Experimental: B
Drug: Cymbalta
30mg/cap 30~60mg/QD
Experimental: C
Drug: Placebo
1~2#/cap QD

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The primary outcome of interest will be the differences of averaged reduction of negative symptom scores among 3 groups compared by Analysis of Variance (ANOVA).
Time Frame: 2010/12
2010/12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
A decrease of 2 or more in the items of N2 or N4 will be indicated as improvement, and the proportion of subjects meeting this improvement criterion will also be compared among three groups by Chi-square statistics
Time Frame: 2010/12
2010/12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Taiwan University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Liu Chih-Min, MD, National Taiwan University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2010

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2011

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 28, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 2, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2010

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2010

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 200907058M

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