Trehalose as add-on Therapy in Bipolar Depression
Condition: Bipolar Disorder; Bipolar Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      This is an investigator-initiated parallel group pilot study. All patients will give a signed
      informed consent prior to initiation of any study procedure.

      Study setting: This unicentric pilot study will be carried out at the Bipolar Disorder
      Programme of the Hospital Clinic, University of Barcelona. Over 700 Bipolar Disorder patients
      are currently treated by Bipolar Disorders Program of the Hospital Clinic and University of
      Barcelona, a tertiary center providing integrated care for patients from a specific catchment
      area as well as difficult-to-treat bipolar patients derived from all over Spain, as already
      described elsewhere.

      Patients are considered to be enrolled in the study when they sign the informed consent.
      Patients are considered to be randomized when they are assigned to receive either trehalose
      or maltose. It is expected that at least 60 patients will be randomly assigned in a 1:1 ratio
      of trehalose 70g to placebo (maltose 70g). Patients will receive no economic compensation for
      their participation in the study.

      Patients will be evaluated at baseline and at weeks 2, 4 and 6. At baseline, patients will
      receive explanations regarding the study; after signing the informed consent patients will be
      interviewed by the study psychiatrist and will be administered the study scales M.I.N.I.
      International Neuropsychiatric Interview-Plus (MINI-Plus), Montgomery-Asberg Depression
      Rating Scale (MADRS), Hamilton Rating scale for Depression (HAMD), Clinical Global
      Impression-Bipolar Disorder (CGI-BP), World Health Organization-well being (WHO-wb),
      Functioning Assessment Short Test (FAST), Cognitive complaints in bipolar disorder rating
      assessment (COBRA). Furthermore, patients will undergo routine blood analysis including
      glycaemia, thyroid function (T3, T4, TSH) as well as lithaemia, at baseline and at week 6. At
      weeks 2 and 4 patients will be administered MADRS, HAMD, CGI-BP, WHO-wb and FAST scales, and
      eventual side effects will be recorded. At week 6, patients will be interviewed and MADRS,
      HAMD, CGI-BP, and FAST and will be administered and side effects recorded. At the final visit
      (week 6), patients will undergo a clinical interview, followed by administration of MADRS,
      CGI-BP, WHO-wb, COBRA and FAST scales. Full blood analysis will be performed.
    

Intervention name(s): Trehalose; Maltose
Intervention type(s): Drug; Drug
Intervention description(s): Trehalose 70g/die; Maltose 70g/die
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment