Brain Derived Neurotrophic Factor as a Predictor of Response to Treatment in Bipolar Depression and Mania
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First Received Date ICMJE | April 9, 2009 | ||||||||
Last Updated Date | February 15, 2011 | ||||||||
Start Date ICMJE | March 2009 | ||||||||
Estimated Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Hamilton depression raing scale and young mania rating scale [ Time Frame: 16 weeks ] [ Designated as safety issue: No ] | ||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | Complete list of historical versions of study NCT00879632 on ClinicalTrials.gov Archive Site | ||||||||
Current Secondary Outcome Measures ICMJE |
Serum BDNF levels as predictor of response to treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ] | ||||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Outcome Measures ICMJE | |||||||||
Original Other Outcome Measures ICMJE | |||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Brain Derived Neurotrophic Factor as a Predictor of Response to Treatment in Bipolar Depression and Mania | ||||||||
Official Title ICMJE | Brain Derived Neurotrophic Factor as a Predictor of Response to Treatment in Bipolar Depression and Mania: 16-weeks Follow-up Study | ||||||||
Brief Summary | There is sound evidence that quetiapine is effective in the treatment of manic and depressive episodes associated with Bipolar Disorder (BD) (Yatham et al 2006). However, even with the development of effective new treatment options, not all patients respond to treatments available. Biological markers have been investigated as predictors of response to treatment and of remission of symptoms. This would explain in part the individual's differences in the response to treatment, taking into account the genetic variability plus environmental factors influencing specific biological markers. A potential biological marker of response to treatment in BD would be the levels of neurotrophins, as they are, in fact, altered during acute mood episodes (Cunha et al 2006). Among neurotrophins, the Brain-Derived Neurotrophic Factor (BDNF) has been repeatedly and consistently reported to be associated with BD physiopathology (Post 2007). Furthermore, medications that are known to be effective in BD, like lithium and divalproex, increase BDNF levels. |
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Detailed Description | There is sound evidence that quetiapine is effective in the treatment of manic and depressive episodes associated with Bipolar Disorder (BD) (Yatham et al 2006). However, even with the development of effective new treatment options, not all patients respond to treatments available. Biological markers have been investigated as predictors of response to treatment and of remission of symptoms. This would explain in part the individual's differences in the response to treatment, taking into account the genetic variability plus environmental factors influencing specific biological markers. A potential biological marker of response to treatment in BD would be the levels of neurotrophins, as they are, in fact, altered during acute mood episodes (Cunha et al 2006). Among neurotrophins, the Brain-Derived Neurotrophic Factor (BDNF) has been repeatedly and consistently reported to be associated with BD physiopathology (Post 2007). Furthermore, medications that are known to be effective in BD, like lithium and divalproex, increase BDNF levels. Diverse sources of evidence provide support to the alteration of BDNF in mood disorders:
Prediction of drug treatment response based on variation in genetic make up is a rapidly growing area. However, few studies examined the association between single nucleotide polymorphisms and drug response in bipolar disorder. The design of this study offers a unique opportunity to examine genetic predictors of drug response. Interestingly, a single nucleotide polymorphism at nucleotide196 (G/A) in the human BDNF gene at codon 66 (Val66Met) have been reported to be associated with a predisposition to BD in family-based studies (Rybakowski et al 2006, Green et al 2006). In humans, this polymorphism produces a valine - to - methionine substitution in the proBDNF protein and reduces the trafficking and secretion of BDNF protein. This is relevant because it has been estimated that 20-30% of the human population is heterozygous for the Met polymorphism of BDNF. Furthermore, there are consistent findings in BD regarding the association of Val66Met polymorphism of BDNF gene with prefrontal cognitive impairment, which was recently confirmed in a large sample of bipolar subjects (Rybakowski et al 2006). In addition, crosssectional studies showed that the polymorphism of BDNF gene (Val66Met) was associated with response to lithium prophylaxis, but findings were not universal (Rybakowski et al 2005, Masui et al 2006). However, there is a need for prospective studies in order to confirm these findings. It is possible that a single polymorphism of BDNF gene would have a negative impact of BDNF levels and, consequently, a negative impact in the response to treatment. Despite consistent evidence of changes in BDNF levels during mood episodes and treatment, one important aspect remains unknown: Whether the change in BDNF levels is required for treatment response and whether the magnitude of change happens in portion with the response to treatment and remission of symptoms. The hypothesis for this project is that those patients who have a good response to treatment are the same ones who show the greater increase in BDNF levels earlier in the course of treatment, and who are less likely to present a polymorphism of BDNF gene. Given this context, we aim to investigate BDNF levels prospectively in patients with BD, before, during and after the treatment with quetiapine and compare measures with response to treatment, as indicated by remission in symptoms. We also aim to investigate the polymorphism of BDNF gene (Val66Met) and its correlation with BDNF serum levels and treatment response. |
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Study Type ICMJE | Observational | ||||||||
Study Design ICMJE | Observational Model: Cohort Time Perspective: Prospective |
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Biospecimen | Retention: Samples With DNA Description: SERUM, DNA, PLASMA |
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Sampling Method | Non-Probability Sample | ||||||||
Study Population | Bipolar disorders patients during acute mania or depression using treatment as usual |
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Condition ICMJE | BIPOLAR DISORDER | ||||||||
Intervention ICMJE | |||||||||
Study Group/Cohort (s) |
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Publications * | |||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE | 200 | ||||||||
Estimated Completion Date | September 2011 | ||||||||
Estimated Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||||||
Ages | 18 Years to 65 Years | ||||||||
Accepts Healthy Volunteers | Yes | ||||||||
Contacts ICMJE |
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Location Countries ICMJE | Brazil | ||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT00879632 | ||||||||
Other Study ID Numbers ICMJE | 07456 | ||||||||
Has Data Monitoring Committee | No | ||||||||
Responsible Party | Flavio Kapczinski, Hospital de clinicas de porto alegre | ||||||||
Study Sponsor ICMJE | Hospital de Clinicas de Porto Alegre | ||||||||
Collaborators ICMJE | National Alliance for Research on Schizophrenia and Depression | ||||||||
Investigators ICMJE |
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Information Provided By | Hospital de Clinicas de Porto Alegre | ||||||||
Verification Date | February 2011 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |