Trehalose as add-on Therapy in Bipolar Depression

#14t-012

The ongoing research on bipolar disorder (BD) has highlighted its pervasive and debilitating nature, characterized by lifelong recurrent episodes and residual intraepisodic symptomatology. Epidemiologic, comorbidity, cost-of illness, and mortality studies have reported dramatic illness-associated morbidity and premature mortality in bipolar patients. The efficacy and safety of antidepressant drug treatment in BD is the subject of long-standing debate based on a scientific literature that is limited and inconsistent. The evidence base for the use of antidepressant drugs in BD is strikingly weak, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. The need to develop new agents for the treatment of depression, and in particular bipolar depression, with better efficacy and/or tolerability, remains unmet. In the past years there has been increasing interest in the health benefits of supplemental and/or dietary substances in the treatment and prevention of depression. The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioural beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs. In fact, trehalose may have antidepressant-like properties and that the trehalose induced behavioral changes are possibly related to trehalose effects to enhance autophagy. Furthermore, preliminary data indicates that trehalose also augments lithium effects in animal models (mice). Based on this hypothesis, this project aims to conduct a study to assess the efficacy and tolerability of trehalose as adjunctive treatment to lithium in bipolar depression.

2016-06-01

2022-10-01

2022-10-01

Completed

Early phase I

60

Inclusion Criteria: * Bipolar I and II patients aged between 18 and 65. * Bipolar disorder type I or II and a current major depressive episode (Montgomery-Asberg Depression Rating Scale (MADRS) ≥18. * Clinical Global Impression-Bipolar version (CGI-BP)≥4. * All patients need to be receiving lithium at a steady dose (0.5-1.2 mmol/L) during at least 2 weeks prior to the study. * Other mood stabilizers added to lithium are permitted but at steady dose during at least 2 weeks prior to the study. * Other psychopharmacological treatments should be at stable dose 2 weeks prior to the study. Exclusion Criteria: * Exclusion criteria will be the presence of psychotic features, severe suicidal ideation (score of ≥5 on item 10 of MADRS). * A severe personality disorder suggesting noncompliance. * Diabetes Mellitus, any severe neurologic or other somatic illness and the use of somatic medication that could influence the mood.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 60, 'type': 'ACTUAL'}}

2023-02-08