BIPOLAR DISORDER | Brain Derived Neurotrophic Factor as a Predictor of Response to Treatment in Bipolar Depression and Mania: 16-weeks Follow-up With Quetiapine XR
BIPOLAR DISORDER research study
What is the primary objective of this study?
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.
Who is eligible to participate?
Inclusion Criteria: 1. Provision of written informed consent 2. A diagnosis of Bipolar Disorder I by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition revised (DSM-IV-TR) 3. Males and females aged 18 to 65 years 4. Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotrophin (HCG) test at enrolment 5. Able to understand and comply with the requirements of the study 6. Currently experiencing a manic, depressive or mixed mood episode, according to DSM-IV-TR. Patients must have a clear DSM-IV diagnosis, confirmed by SCID interview (Structured Clinical Interview for DSM disorders). Exclusion Criteria: 1. Pregnancy or lactation 2. Any DSM-IV Axis I disorder not defined in the inclusion criteria 3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others 4. Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator 5. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir 6. Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids 7. Currently on psychotropic medication or administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation. Wash-out of minimum of 2 weeks will be required for intake. Fluoxetine use or depot antipsychotics will require 6 weeks of wash-out prior to intake. 8. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria 9. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment 10. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment 11. Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator 12. Involvement in the planning and conduct of the study 13. Previous enrolment in the present study. 14. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements 15. A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria: - Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%. - Admitted to hospital for treatment of DM or DM related illness in past 12 weeks. - Not under physician care for DM - Physician responsible for patient's DM care has not indicated that patient's DM is controlled. - Physician responsible for patient's DM care has not approved patient's participation in the study - Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks. - Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:quetiapineUse of quetiapine for 16 weeks in acute mania and depression
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
1Use of quetiapine
Start Date: March 2009
Completed Date: September 2011
Phase: Phase 3
Primary Outcome: Efficacy of quetiapine as a treatment for acute mania and depression, and of as a manutence treatment.
Secondary Outcome: Assess the pharmacodynamics of quetiapine by neurotrophins in blood samples.
Study sponsors, principal investigator, and references
Principal Investigator: FLAVIO KAPCZINSKI, MD, PHD
Lead Sponsor: Hospital de Clinicas de Porto Alegre