Longitudinal Study on the Neuroprotective and Neurotrophic Effects of Lithium

Bipolar Disorder Clinical Trial

Official title:

Longitudinal Study on the Neuroprotective and Neurotrophic Effects of Lithium in Bipolar Disorder: Identification of Cellular and Molecular Targets Clinically Relevant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01919892
• Other study ID #: Lithium001
• Secondary ID: 09/14891-9
• Status: Completed
• Phase: Phase 4
• First received: July 10, 2013
• Last updated: August 6, 2013
• Start date: September 2010
• Est. completion date: November 2012

Study information

• Verified date: August 2013
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

Thirty subjects with a DSM-IV (Diagnostic and Statistical Manual, fourth version)diagnosis of BPD during a depressive or hypomanic episode will be divided in two groups according to age and time of illness. All patients will receive lithium (flexible therapeutic dose) for 6 weeks and improvement will be evaluated weekly using depression and mania rating scales; this study also objectives to identify state/trait markers and predictors of response.

Description:

Mood disorders are the most prevalent psychiatric, presenting chronic course and high morbidity, affecting 10-15% of population. Diverse structural, functional and biochemical cerebral changes described in the pathophysiology of mood disorders, in special Bipolar Disorder (BPD), have been associated with impairments in neuroprotective mechanisms and cellular resilience. However, the clinical relevance of these pathophysiological findings have been rarely addressed. Meanwhile, lithium has been considered the most used mood stabilizer worldwide, showing significant efficacy in the treatment of manic and depressive episodes, as well as in the prevention of suicide and maintenance. Several studies have demonstrated significant neuroprotective and neurotrophic effects induced by lithium treatment in diverse cellular and molecular targets, but again, few is known about the potential association between these cerebral effects and the its therapeutic clinical efficacy induced by this proof of concept agent. The present project aims to investigate brain levels of lithium using magnetic resonance spectroscopy (7Li-MRS) and its association with different markers of neuronal viability such as n-acetyl-aspartate (using 1-hydrogen-MRS), as well as peripheral markers of mitochondrial, endoplasmic reticulum and neurotrophic factors activity, all highly implicated in the pathophysiology of BD. The investigator has been working in this area in the last ten years, in which the last three and a half in the Lab of Molecular Pathophysiology and Experimental Therapeutics, National Institute of Mental Health (NIMH), National Institutes of Health. The candidate is looking forward to establish appropriate structure to develop a "Research Center for the Study of Neuroplasticity and Neuroprotection in Psychiatric Disorders" in the Institute of Psychiatry, University of Sao Paulo, Brazil. Overall, the study on the neuroplasticity-mediated pathophysiological basis of BPD implicated in the clinical presentation and outcome may shed light on the development of new, improved therapeutics for this and other devastating psychiatric disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• outpatients

• 18-45 yo

• DSM-IV diagnosis of bipolar disorder (BD-I or BD-II)

• current depressive episode based on the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders(SCID-I)

• Hamilton Depression Rating Scale Score (HAM-D) =18

Exclusion Criteria

• Medical and psychiatric Comorbidity

• more than 5 years of disease duration

• presence of rapid cycling

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder

Intervention

Drug:
• Lithium

Locations

Country	Name	City	State
Brazil	Institute of Psychiatry, University of Sao Paullo	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Young Mania Rating Scale	Evaluation of potential switch process to mania in Bipolar Disorder	6 week	No
Primary	Hamilton Depression Rating Scale (HAM-D)		6 week	No
Secondary	Montgomery Asberg Depression Rating Scale (MADRS)		6 week	No