Ignite Creation Date:
2024-05-05 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00269334
Status:
UNKNOWN
Last Update Posted:
2005-12-23
First Post:
2005-12-22
Brief Title:
Clinical Pharmacogenomics of Antidepressant Response
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
Phase 4 Study of Clinical Pharmacogenomics of Antidepressant Response
Status:
UNKNOWN
Status Verified Date:
2005-12
Last Known Status:
NOT_YET_RECRUITING
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:
None
Brief Summary:
The study includes two components1 cross-sectional Study I and 2 longitudinal treatment trial Study II The cross-sectional component will include all subjects initially recruited for the parent project Genotyping characteristics will be compared with clinical status ie recovered vs symptomatic The treatment trial component one will include a subset of the subjects n 400 who remain significantly depressed They will be randomly assigned to 8-weeks of treatment with either citalopram or paroxetine With such a design we wish to test the following hypotheses
Ⅰ Depressed patients with the short variant of the serotonin transporter 5HTTLPR will respond faster and better to antidepressants compared to their counterparts with the long variant Concurrently patients with the 5-HTT Stin2 1212 allele will also show better response as compared to those with the 1012 allele
Ⅱ Depressed patients who are homozygous for deficient or less active CYP2D6 or CYP2C19 enzymes will be more likely to show treatment emergent side effects compared to subjects with the wildtype alleles Specifically in Study II CYP2D6 polymorphism will predict PAR but not CIT side effects and CYP2C19 polymorphism will be associated with CIT but not PAR side effects
Ⅰ Depressed patients with the short variant of the serotonin transporter 5HTTLPR will respond faster and better to antidepressants compared to their counterparts with the long variant Concurrently patients with the 5-HTT Stin2 1212 allele will also show better response as compared to those with the 1012 allele
Ⅱ Depressed patients who are homozygous for deficient or less active CYP2D6 or CYP2C19 enzymes will be more likely to show treatment emergent side effects compared to subjects with the wildtype alleles Specifically in Study II CYP2D6 polymorphism will predict PAR but not CIT side effects and CYP2C19 polymorphism will be associated with CIT but not PAR side effects
Detailed Description:
Despite remarkable progress in recent decades in modern psychopharmacotherapy patients vary substantially in their response to antidepressants ranging from total remission to complete treatment failure Adverse effects often bothersome and occasionally life-threatening continue to represent significant challenges to patients and clinicians Mechanisms responsible for such variability remain poorly understood In addition although less appreciated substantial cross-ethnic variations in psychotropic responses often exist Recent developments in the field of pharmacogenetics indicate that genetic factors may account for a large part of these differences in response Specific genetic polymorphisms affecting the function of the serotonin SERT system has been postulated to predict the effect of antidepressants Similarly genetic mutations have been shown to exert a predominant influence on the expression of a number of drug-metabolizing enzymes including most of the cytochrome P-450 enzymes eg CYP2C19 and CYP3A4 that are responsible for the biotransformation of most antidepressants Polymorphisms of genes controlling these enzymes have been found to be strongly associated with the propensity for various kinds of side effects Capitalizing on these new developments the proposed study will examine the predictive value of some of these genetic polymorphisms in 400 patients with DSM-IV major depression prospectively treated with citalopram CIT It is postulated that mutations affecting the function of SERT will predict responses to CIT polymorphism of CYP2C19 will be associated with the side effect profiles and pharmacokinetics of CIT The proposed study represents an extension and replication of a 5-year NIHNIMH collaborative project that had designed and initiated in 2001 by the PI which is currently ongoing at three sites in the US Ethnic Variations in Antidepressant Response 1 R01 MH62421 1R01MH626761R01MH62531 0701 - 0606 In the original study the inclusion of the two comparison groups African Americans and Caucasians whose genetic mutation patterns diverge significantly from each other will allow us to examine how these differences affect their antidepressant response patterns and whether the associations are replicable across ethnicity Results will be pooled with those derived from other sites and will represent a rare opportunity to compare findings across Taiwanese African American and Caucasian subjects with comparable diagnosis and treated with an identical protocol
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 |
|---|---|---|---|
| NSC 94-2314-B-400 -001 - | None | None | None |