Overview

This trial is active, not recruiting.

Condition bipolar disorder
Treatments tianeptine, placebo
Phase phase 3
Sponsor Hospital de Clinicas de Porto Alegre
Collaborator Conselho Nacional de Desenvolvimento Científico e Tecnológico
Start date March 2009
End date May 2013
Trial size 13 participants
Trial identifier NCT00879372, 08-145

Summary

One of the main challenges in the treatment of Bipolar Disorder (BD) is to achieve better functioning outcomes after syndromal recovery. Even treatment-responsive patients, who remain symptomatically well for extended periods of time, frequently demonstrate sub-threshold symptoms and continuing psychosocial morbidity and cognitive impairment. The cognitive impairment that persists during interepisode periods stands out as a major correlate of functional impairment, and may be a core aspect of the BD pathophysiology.

In this context, tianeptine stands out as a therapeutic agent with unique properties, which match most of the conditions found in BD.

This is an enriched maintenance study of the use of tianeptine as an adjunctive therapy in bipolar depression. All participants will receive tianeptine in an open label manner for a period of two months, following which they will be assigned randomly to the treatment with tianeptine or placebo in a double-blind fashion for six months. All patients will remain on treatment as usual for the duration of the trial. Along with clinical response, the investigators will prospectively evaluate the improvement in working and declarative memory, two cognitive prefrontal- and hippocampus-dependent processes, respectively, and the effects of tianeptine on serum BDNF levels.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Placebo Comparator)
Placebo
placebo
Placebo 12.5 mg TID
(Active Comparator)
Tianeptine
tianeptine Stablon (Servier)
tianeptine 12,5mg TID

Primary Outcomes

Measure
Improvement in mood symptoms (Hamilton depression rating scale)
time frame: @ 4 weeks and @ 8 months

Secondary Outcomes

Measure
Cognitive improvement
time frame: @ 4 weeks and @ 8 months

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

Inclusion Criteria: - To be included patients will be required to: - Meet DSM-IV criteria for bipolar disorder types I or II - Have current symptoms of depression, with a MADRS score over 12 at baseline - Have the capacity to consent to the study and comply with the study procedures - Use effective contraception in the case of women of childbearing age - Patients will need to be in a stable dose of mood stabilizer for at least one month prior to randomization. Exclusion Criteria: - Exclusion from the trial includes: - Patients with a well defined or suspected clinically unstable systemic medical conditions - Pregnant or lactating women - Patients who are currently taking augmentation medications or supplementation - Patients who do not tolerate the use of tianeptine - Inability to comply with either the requirements or informed consent of the treatment protocol. - Withdrawal criteria: - Withdrawal from the trial will take place whenever: - Patients stop taking medication or are deemed as non compliant by the attending physician - Patients stop taking contraceptives of become pregnant - Dose changes or additions/exclusions to existing medication - patients will be kept in the trial, but such changes will be computed as a primary outcome - Serious adverse reactions - Withdrawal of consent by the patient - Hospitalization

Additional Information

Official title Double Blind,Randomized, Placebo Controlled Trial of Adjunctive Tianeptine in the Treatment of Bipolar Depression
Principal investigator Flavio Kapczinski, MD,PhD
Description One of the main challenges in the treatment of Bipolar Disorder (BD) is to achieve better functioning outcomes after syndromal recovery. Available treatments are reasonably effective in reducing acute symptoms, but many times the syndromal recovery is not accompanied by the restoration of functioning capabilities. This is particularly true for bipolar depression, which is responsible for most of the burden associated with BD. Even treatment-responsive patients, who remain symptomatically well for extended periods of time, frequently demonstrate sub-threshold symptoms and continuing psychosocial morbidity and cognitive impairment. The cognitive impairment that persists during interepisode periods stands out as a major correlate of functional impairment, and may be a core aspect of the BD pathophysiology. Beyond that, cognitive impairment worsens with cumulative episodes. Functional and morphometric studies have shown changes in amygdala, hippocampus and prefrontal cortex of patients with bipolar disorder. Effective treatments for bipolar disorder, such as lithium and divalproex, have proved to prevent cellular atrophy, to have antiapoptotic properties and to increase BDNF levels. Findings from neuropathological studies have confirmed reduction and dysgenesis of neuronal cell lines in the hippocampus in bipolar disorder. Ultimately, a main challenge in the treatment of BD is translating the knowledge of neuronal plasticity and neurobiology of the illness into novel therapeutic options. In this context, tianeptine stands out as a therapeutic agent with unique properties, which match most of the conditions found in BD. The neurochemical properties of tianeptine vary from those of other tricyclic and non-tricyclic antidepressants. Noteworthy, none of current available medications for BD showed all these features: 1) tianeptine exert opposite effects than chronic stress in neurons, increasing neuroprotective factors what may help to quench the cycle of affective episode recurrence and neural and deterioration; 2) tianeptine affects neuroplasticity in the hippocampus and have been reported to increase dendritic lengths; 3) tianeptine increases BDNF levels in the amygdala; 4) tianeptine attenuated stress-induced glutamate release in amygdala; 5) tianeptine has anticonvulsant properties via adenosinergic A1 receptors; 6) tianeptine has analgesic effects. In the present research project, we plan on conducting an enriched maintenance study of the use of tianeptine as an adjunctive therapy in bipolar depression. All participants will receive tianeptine in an open label manner for a period of two months, following which they will be assigned randomly to the treatment with tianeptine or placebo in a double-blind fashion for six months. All patients will remain on treatment as usual for the duration of the trial. This trial will allow the investigation of the efficacy and tolerability of tianeptine 37.5mg/day as an adjunctive treatment of bipolar depression and its impact on clinical variables associated with the aftermath of a bipolar depression episode. Considering that tianeptine is approved to be used orally in humans and has been on the market for depression, a low risk intervention using a novel approach may be provided by this clinical trial. Along with clinical response, we will prospectively evaluate the improvement in working and declarative memory, two cognitive prefrontal- and hippocampus-dependent processes, respectively, and the effects of tianeptine on serum BDNF levels.
Trial information was received from ClinicalTrials.gov and was last updated in October 2013.
Information provided to ClinicalTrials.gov by Hospital de Clinicas de Porto Alegre.