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Efficacy of Adjunctive Tianeptine in the Treatment of Bipolar Depression

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Stanley Medical Research Institute
Information provided by (Responsible Party):
Flavio Kapczinski, Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier:
NCT00879372
First received: April 9, 2009
Last updated: October 5, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: tianeptine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double Blind,Randomized, Placebo Controlled Trial of Adjunctive Tianeptine in the Treatment of Bipolar Depression

Resource links provided by NLM:


Further study details as provided by Hospital de Clinicas de Porto Alegre:

Primary Outcome Measures:
  • Improvement in mood symptoms (Hamilton depression rating scale) [ Time Frame: @ 4 weeks and @ 8 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive improvement [ Time Frame: @ 4 weeks and @ 8 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 13
Study Start Date: March 2009
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Placebo
Drug: Placebo
Placebo 12.5 mg TID
Active Comparator: 2
Tianeptine
Drug: tianeptine
tianeptine 12,5mg TID
Other Name: Stablon (Servier)

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879372

Locations
Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, RS, Brazil, 90035-003
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Stanley Medical Research Institute
Investigators
Principal Investigator: Flavio Kapczinski, MD,PhD Hospital de Clinicas de Porto Alegre and UFRGS
  More Information

No publications provided

Responsible Party: Flavio Kapczinski, PhD, Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier: NCT00879372     History of Changes
Other Study ID Numbers: 08-145
Study First Received: April 9, 2009
Last Updated: October 5, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Hospital de Clinicas de Porto Alegre:
Bipolar Disorder
cognitive impairment
depression

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Behavioral Symptoms
Mental Disorders
Mood Disorders
Tianeptine
Antidepressive Agents
Antidepressive Agents, Tricyclic
Central Nervous System Agents
Pharmacologic Actions
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014