Ignite Creation Date:
2024-05-06 @ 2:38 AM
Last Modification Date:
2024-10-26 @ 11:21 AM
Study NCT ID:
NCT02095938
Status:
UNKNOWN
Last Update Posted:
2014-03-26
First Post:
2014-03-20
Brief Title:
Association of Amisulpride Response in Schizophrenia With Brain Image
Sponsor:
CHA University
Organization:
CHA University
Study Overview
Official Title:
Association of the Amisulpride Treatment Response in Patients With Schizophrenia With the Findings of Brain Structural Magnetic Resonance Imaging
Status:
UNKNOWN
Status Verified Date:
2014-03
Last Known Status:
ENROLLING_BY_INVITATION
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ARB
Brief Summary:
1 Study rationale - Nielsen et al reported that after 6 weeks of amisulpride treatment patients with schizophrenia showed an increase in the anticipation-related functional MRI signal This suggested that amisulpride could affect the brain structures and that responses to amisulpride could be associated by the brain structures as seen previous studies about treatment response to antipsychotics and brain structures But to date no study has examined the impact of brain structure alterations on amisulpride treatment for schizophrenia and its potential clinical significance
2 Study Objectives 2-1 Primary To show the differences of the baseline brain structures on the structural MRI between the Solian treatment responders and the non-responders 2-2 Secondary To show the differences of the baseline polymorphisms of COMT and BDNF with molecular genetic analysis between the Solian treatment responders and the non-responders responder defined by PANSS To find out the correlates of baseline brain structures with symptom severity of schizophrenia at baseline symptom severity defined by CGI-S and PANSS To assess psychotic symptom improvement after 8th week of Solian treatment using PANSS SANS SAPS and CGI To assess safety after 8th week of Solian treatment with Barnes Akathisia Scale Simpson-Angus scale and vital signs To report all serious adverse event within 24hrs regardless of relationship to investigational product
3 Study Design Prospective Open label Interventional Controlled
4 Evaluation Criteria
5-1 Primary endpoints Brain structures on the structural MRI will be observed before the treatment starts Based on the clinical response after treatment patients will be divided in the two different groups as follow and their baseline brain structure of will be compared Treatment responders and non-responders
5-2 Secondary endpoints The relationship of baseline brain structures with symptom severity of schizophrenia Severity will be determined by CGI-S and PANSS at baseline The differences of the polymorphisms of COMT and BDNF with molecular genetic analysis using patients peripheral blood especially leukocytes between the treatment responders and the non-responders Efficacy - PANSS SANS SAPS CGI Safety - Barnes akathisia scale Simpson-Angus scale Vital signs
2 Study Objectives 2-1 Primary To show the differences of the baseline brain structures on the structural MRI between the Solian treatment responders and the non-responders 2-2 Secondary To show the differences of the baseline polymorphisms of COMT and BDNF with molecular genetic analysis between the Solian treatment responders and the non-responders responder defined by PANSS To find out the correlates of baseline brain structures with symptom severity of schizophrenia at baseline symptom severity defined by CGI-S and PANSS To assess psychotic symptom improvement after 8th week of Solian treatment using PANSS SANS SAPS and CGI To assess safety after 8th week of Solian treatment with Barnes Akathisia Scale Simpson-Angus scale and vital signs To report all serious adverse event within 24hrs regardless of relationship to investigational product
3 Study Design Prospective Open label Interventional Controlled
4 Evaluation Criteria
5-1 Primary endpoints Brain structures on the structural MRI will be observed before the treatment starts Based on the clinical response after treatment patients will be divided in the two different groups as follow and their baseline brain structure of will be compared Treatment responders and non-responders
5-2 Secondary endpoints The relationship of baseline brain structures with symptom severity of schizophrenia Severity will be determined by CGI-S and PANSS at baseline The differences of the polymorphisms of COMT and BDNF with molecular genetic analysis using patients peripheral blood especially leukocytes between the treatment responders and the non-responders Efficacy - PANSS SANS SAPS CGI Safety - Barnes akathisia scale Simpson-Angus scale Vital signs
Detailed Description:
1 Study rationale 1-1
Predicting the treatment response of antipsychotic drug in schizophrenia patients has been an issue in psychiatry However it is not clear if the findings of structural magnetic resonance imaging MRI such as brain gray matter volumes and white matter connectivities are related to the treatment response of antipsychotic drugs
The cognitive and behavioural symptoms of patients with schizophrenia are hypothesized to involve a disruption of neuronal interactions resulting in dysfunctional cognitive integration Friston et al 1995 1996 This hypothesis is supported by reports about a decrease in white matter anatomic connections Mitelman et al 2006 Skudlarski et al 2010 Zalesky et al 2011 and brain structure alterations especially decrease in volumes of specific brain regions for patients with schizophrenia Several studies of brain connectivity have shown that functional connectivity depends strongly on the underlying anatomic structure Sporns O et al 2004 At the anatomic level the pathology of schizophrenia has been related to a wide range of anatomic abnormalities including ventricular enlargement associated with anomalous neurodevelopment or neurodegenerative alterations Shenton ME et al 2001 And schizophrenia is likely to be the result of both general and specific localized changes in both grey and white matter Knochel C et al 2012 Konrad A et al 2008 Savas HA et al found that responders to risperidone had greater hippocampal volumes than patients who failed to respond to risperidone Savas HA et al 2002 Vicente M et al found an inverse association between striatal size and the degree of clinical improvement and a direct association between the degree of insular volume deficit and its improvement The non-responders to risperidone or olanzapine showed a significant decrease in their left rectal gyrus as compared with the responder group Vicente M et al 2010
Nielsen et al reported that after 6 weeks of amisulpride treatment patients with schizophrenia showed an increase in the anticipation-related functional MRI signal Nielsen et al 2012 This suggested that amisulpride could affect the brain structures and that responses to amisulpride could be associated by the brain structures as seen previous studies about treatment response to antipsychotics and brain structures But to date no study has examined the impact of brain structure alterations on amisulpride treatment for schizophrenia and its potential clinical significance
2 Study type Clinical Study Phase IV
3 Number of centers a single center in Korea
4 Number of subjects N 20 patients
5 Study duration and dates format date ddmmmyyyy 5-1 Protocol planned date 01Apr2013 5-2 First patient In 01Nov2013 5-3 Last patient In 01Oct2015 5-4 Last patient Out 01Dec2015 5-5 Estimated enrollment duration 2 years 5-6 Estimated average treatment duration 8 weeks 5-7 Database lock planned date 15Dec2015 5-8 Estimated ReportPublication date 31Dec2015
6 Indication Schizophrenia
7 Study Objectives Primary Most Important Secondary
7-1 Primary To show the differences of the baseline brain structures on the structural MRI between the Solian treatment responders and the non-responders 7-2 Secondary
To show the differences of the baseline polymorphisms of COMT and BDNF with molecular genetic analysis between the Solian treatment responders and the non-responders responder defined by PANSS
To find out the correlates of baseline brain structures with symptom severity of schizophrenia at baseline symptom severity defined by CGI-S and PANSS
To assess psychotic symptom improvement after 8th week of Solian treatment using positive and negative syndrome scale PANSS scale for the assessment of negative symptoms SANS scale for the assessment of positive symptoms SAPS and clinical global impression scale CGI
To assess safety after 8th week of Solian treatment with Barnes Akathisia Scale Simpson-Angus scale and vital signs
To report all serious adverse event SAE within 24hrs regardless of relationship to investigational product SAE or expedited reports are completed including death Requiringprolonging hospitalization Congenital anomalyBirth defect Life-threatening Persistentsignificant disabilityincapacity A procedure result only if symptomatic considered by the investigator as clinically significant or meaningful or leading to permanent investigational product discontinuation or requiring corrective treatment A symptomatic overdose A pregnancy AESI adverse event special interest with immediate notification in AEs serious or non-serious that need to be monitored documented and managed in a pre-specified manner described in the protocol
8 Inclusion Criteria
8-1 between 21 and 60 years of age 8-2 diagnosed with schizophrenia based on the Structured Clinical Interview for DSM-IVSCID 8-3 first or second episode of schizophrenia patient 8-4 the presence of positive or negative symptoms or both resulting in illness of at least mild severity 3 on the Clinical Global Impression CGI severity scale
9 Exclusion Criteria
9-1 evidence of organic mental disorder or mental retardation 9-2 severe drug or alcohol dependence that required inpatient treatment andor detoxification 9-3 other conditions such as a serious medical condition a history of bipolar or schizoaffective disorder suicidality possibility of pregnancy lactation or inabilityunwillingness to use contraception 9-4 contraindicated with Solian by the product label
10 Study Design Prospective Open label Interventional Controlled
11 Treatments
11-1 Study medication - Solian and there is no comparator medication 11-2 Amisulpride Solian will be orally administered once or twice daily after meal intake for 8 weeks Patients initially will receive a low dose of amisulpride 200-400mgday The dosage may be adjusted to between 400 and 800mgday according to the clinical decision by treating physician
11-3 For efficacy assessment psychotic symptoms will be assessed on baseline and 8th week by psychiatrists with positive and negative syndrome scale PANSS scale for the assessment of negative symptoms SANS scale for the assessment of positive symptoms SAPS and clinical global impression scale CGI
11-4 For safety assessment Barnes Akathisia Scale Simpson-Angus scale and vital signs will be assessed on 8th week of treatment
11-5 Treatment responders will be defined as patients whose PANSS score reduction by 30 or more and patients whose PANSS score decrease by less than 30 will be assigned to non-responder group
11-6 The investigators will evaluate the differences of gray matter volume and white matter connectivity between responders and non-responders to amisulpride with images from brain 3T magnetic resonance imaging MRI using voxel-based morphometry VBM and tract-based spatial statistics TBSS at baseline To examine a possible association between a specific brain region and response to amisulpride the investigators will use methods based on the definition of regions of interest ROIs
11-7 The investigators will evaluate the polymorphisms of COMT and BDNF with molecular genetic analysis using patients peripheral blood especially leukocytes at baseline One-way analysis of variance ANOVA will be used to assess variations in clinical symptoms and cognitive function according to COMT and BDNF polymorphisms
12 Evaluation Criteria
12-1 Primary endpoints
Brain structures on the structural MRI will be observed before the treatment starts Based on the clinical response after treatment patients will be divided in the two different groups as follow and their baseline brain structure of will be compared
Treatment responders and non-responders Treatment response will be defined as patients whose PANSS score reduce by 30 or more and non-responder as patients whose PANSS score decrease by less than 30 at 8 weeks from baseline
12-2 Secondary endpoints
The relationship of baseline brain structures with symptom severity of schizophrenia Severity will be determined by CGI-S and PANSS at baseline
The differences of the polymorphisms of COMT and BDNF with molecular genetic analysis using patients peripheral blood especially leukocytes between the treatment responders and the non-responders
Efficacy PANSS SANS SAPS CGI on baseline and 8th week
Safety Barnes akathisia scale Simpson-Angus scale Vital signs at 8th week
13 Study Budget 13-1 Total Study Cost euro 13848 euro 1 EUR 1445 KRW 13-2 Y year of Study Outline approval 5539 EUR 13-3 Y1 5539 EUR 13-4 Beyond Y1 2770 EUR
Predicting the treatment response of antipsychotic drug in schizophrenia patients has been an issue in psychiatry However it is not clear if the findings of structural magnetic resonance imaging MRI such as brain gray matter volumes and white matter connectivities are related to the treatment response of antipsychotic drugs
The cognitive and behavioural symptoms of patients with schizophrenia are hypothesized to involve a disruption of neuronal interactions resulting in dysfunctional cognitive integration Friston et al 1995 1996 This hypothesis is supported by reports about a decrease in white matter anatomic connections Mitelman et al 2006 Skudlarski et al 2010 Zalesky et al 2011 and brain structure alterations especially decrease in volumes of specific brain regions for patients with schizophrenia Several studies of brain connectivity have shown that functional connectivity depends strongly on the underlying anatomic structure Sporns O et al 2004 At the anatomic level the pathology of schizophrenia has been related to a wide range of anatomic abnormalities including ventricular enlargement associated with anomalous neurodevelopment or neurodegenerative alterations Shenton ME et al 2001 And schizophrenia is likely to be the result of both general and specific localized changes in both grey and white matter Knochel C et al 2012 Konrad A et al 2008 Savas HA et al found that responders to risperidone had greater hippocampal volumes than patients who failed to respond to risperidone Savas HA et al 2002 Vicente M et al found an inverse association between striatal size and the degree of clinical improvement and a direct association between the degree of insular volume deficit and its improvement The non-responders to risperidone or olanzapine showed a significant decrease in their left rectal gyrus as compared with the responder group Vicente M et al 2010
Nielsen et al reported that after 6 weeks of amisulpride treatment patients with schizophrenia showed an increase in the anticipation-related functional MRI signal Nielsen et al 2012 This suggested that amisulpride could affect the brain structures and that responses to amisulpride could be associated by the brain structures as seen previous studies about treatment response to antipsychotics and brain structures But to date no study has examined the impact of brain structure alterations on amisulpride treatment for schizophrenia and its potential clinical significance
2 Study type Clinical Study Phase IV
3 Number of centers a single center in Korea
4 Number of subjects N 20 patients
5 Study duration and dates format date ddmmmyyyy 5-1 Protocol planned date 01Apr2013 5-2 First patient In 01Nov2013 5-3 Last patient In 01Oct2015 5-4 Last patient Out 01Dec2015 5-5 Estimated enrollment duration 2 years 5-6 Estimated average treatment duration 8 weeks 5-7 Database lock planned date 15Dec2015 5-8 Estimated ReportPublication date 31Dec2015
6 Indication Schizophrenia
7 Study Objectives Primary Most Important Secondary
7-1 Primary To show the differences of the baseline brain structures on the structural MRI between the Solian treatment responders and the non-responders 7-2 Secondary
To show the differences of the baseline polymorphisms of COMT and BDNF with molecular genetic analysis between the Solian treatment responders and the non-responders responder defined by PANSS
To find out the correlates of baseline brain structures with symptom severity of schizophrenia at baseline symptom severity defined by CGI-S and PANSS
To assess psychotic symptom improvement after 8th week of Solian treatment using positive and negative syndrome scale PANSS scale for the assessment of negative symptoms SANS scale for the assessment of positive symptoms SAPS and clinical global impression scale CGI
To assess safety after 8th week of Solian treatment with Barnes Akathisia Scale Simpson-Angus scale and vital signs
To report all serious adverse event SAE within 24hrs regardless of relationship to investigational product SAE or expedited reports are completed including death Requiringprolonging hospitalization Congenital anomalyBirth defect Life-threatening Persistentsignificant disabilityincapacity A procedure result only if symptomatic considered by the investigator as clinically significant or meaningful or leading to permanent investigational product discontinuation or requiring corrective treatment A symptomatic overdose A pregnancy AESI adverse event special interest with immediate notification in AEs serious or non-serious that need to be monitored documented and managed in a pre-specified manner described in the protocol
8 Inclusion Criteria
8-1 between 21 and 60 years of age 8-2 diagnosed with schizophrenia based on the Structured Clinical Interview for DSM-IVSCID 8-3 first or second episode of schizophrenia patient 8-4 the presence of positive or negative symptoms or both resulting in illness of at least mild severity 3 on the Clinical Global Impression CGI severity scale
9 Exclusion Criteria
9-1 evidence of organic mental disorder or mental retardation 9-2 severe drug or alcohol dependence that required inpatient treatment andor detoxification 9-3 other conditions such as a serious medical condition a history of bipolar or schizoaffective disorder suicidality possibility of pregnancy lactation or inabilityunwillingness to use contraception 9-4 contraindicated with Solian by the product label
10 Study Design Prospective Open label Interventional Controlled
11 Treatments
11-1 Study medication - Solian and there is no comparator medication 11-2 Amisulpride Solian will be orally administered once or twice daily after meal intake for 8 weeks Patients initially will receive a low dose of amisulpride 200-400mgday The dosage may be adjusted to between 400 and 800mgday according to the clinical decision by treating physician
11-3 For efficacy assessment psychotic symptoms will be assessed on baseline and 8th week by psychiatrists with positive and negative syndrome scale PANSS scale for the assessment of negative symptoms SANS scale for the assessment of positive symptoms SAPS and clinical global impression scale CGI
11-4 For safety assessment Barnes Akathisia Scale Simpson-Angus scale and vital signs will be assessed on 8th week of treatment
11-5 Treatment responders will be defined as patients whose PANSS score reduction by 30 or more and patients whose PANSS score decrease by less than 30 will be assigned to non-responder group
11-6 The investigators will evaluate the differences of gray matter volume and white matter connectivity between responders and non-responders to amisulpride with images from brain 3T magnetic resonance imaging MRI using voxel-based morphometry VBM and tract-based spatial statistics TBSS at baseline To examine a possible association between a specific brain region and response to amisulpride the investigators will use methods based on the definition of regions of interest ROIs
11-7 The investigators will evaluate the polymorphisms of COMT and BDNF with molecular genetic analysis using patients peripheral blood especially leukocytes at baseline One-way analysis of variance ANOVA will be used to assess variations in clinical symptoms and cognitive function according to COMT and BDNF polymorphisms
12 Evaluation Criteria
12-1 Primary endpoints
Brain structures on the structural MRI will be observed before the treatment starts Based on the clinical response after treatment patients will be divided in the two different groups as follow and their baseline brain structure of will be compared
Treatment responders and non-responders Treatment response will be defined as patients whose PANSS score reduce by 30 or more and non-responder as patients whose PANSS score decrease by less than 30 at 8 weeks from baseline
12-2 Secondary endpoints
The relationship of baseline brain structures with symptom severity of schizophrenia Severity will be determined by CGI-S and PANSS at baseline
The differences of the polymorphisms of COMT and BDNF with molecular genetic analysis using patients peripheral blood especially leukocytes between the treatment responders and the non-responders
Efficacy PANSS SANS SAPS CGI on baseline and 8th week
Safety Barnes akathisia scale Simpson-Angus scale Vital signs at 8th week
13 Study Budget 13-1 Total Study Cost euro 13848 euro 1 EUR 1445 KRW 13-2 Y year of Study Outline approval 5539 EUR 13-3 Y1 5539 EUR 13-4 Beyond Y1 2770 EUR
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| AMISUL06995 | OTHER_GRANT | Handok Inc | None |