None listed
Conditions
Brief summary
Bipolar disorder is a highly debilitating illness characterized by two illness phases - mania and depression. It is the depressive phase that confers the greatest burden of disease and is associated with the highest risk of suicide. Only 3 evidence based medications approved by the Food and Drug Administration (FDA) are available for treating acute bipolar depression. Despite these therapies, patients spend more than half of their symptomatic periods depressed. The failure in bipolar depression treatment discovery is largely due to its complex pathophysiology with many known and unknown biological and environmental factors. Typical drug development paradigms that target single proteins insufficiently address this challenge. We have bypassed this obstacle using an entirely novel in silico approach, which identified trimetazidine as having effects that mimic a combination of current bipolar disorder medications. Trimetazidine’s ability in optimising energy generation dovetails with our research highlighting bipolar depression as a state of decreased energy generation and mania of increased energy generation. Trimetazidine is also highly accessible, affordable, and has regulatory approval to treat angina in India and Europe. It is then logical to clinically evaluate trimetazidine in a double-blind, randomised, placebo-controlled trial in people with bipolar depression. We have assembled a world-class investigator team to test trimetazidine’s efficacy in reducing bipolar depression in a Phase 2 clinical trial to be conducted in India and Spain, as the agent is registered and widely used in those countries. A positive outcome here would have immediate clinical relevance, providing a novel therapy for bipolar depression and providing concrete evidence for a novel mechanism of disease.
Interventions
8 weeks of adjunctive trimetazidine 35 mg oral tablet, twice a day. Treatment adherence will be assessed by tablet count of returned trial medication bottles.
Sponsors
Deakin University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
I. Aged 18-65 years; II. Have a DSM-V diagnosis of bipolar disorder I or II, or bipolar disorder not elsewhere classified (NEC); III. Currently be in a major depressive episode on Structured Clinical Interview for DSM Disorders (SCID-5-RV); IV. Score greater than or equal to 20 on the Montgomery Åsberg Depression Rating Scale (MADRS); V. have the capacity to consent to the study and to follow its instructions and procedures; VI. be using effective contraception if a sexually active woman of a childbearing age; VII. be able to speak, read, write, and understand their national language; VIII. have been on stable pre-existing pharmacological or psychotherapy regimens for 4 weeks prior to study entry (to mitigate the risk of induction of mania all participants will also need to be on an accepted mood stabiliser); IX. Participants will be required to nominate a current treating physician prior to randomization.
Exclusion criteria
I. have a known or suspected active systemic medical disorder; II. have a primary clinical diagnosis of another disorder such as borderline personality disorder, assessed using the SCID-5-RV; III. have a diagnosis of another psychotic disorder and/or current substance use disorder, assessed using the SCID-5-RV; IV. be undergoing electroconvulsive or transcranial magnetic stimulation therapy; V. have contraindications or intolerance or allergy to trimetazidine or any of the trial preparations; VI. have a concurrent enrolment in another psychiatric clinical trial; VII. are pregnant or lactating (participants will be requested to conduct a urine pregnancy test if sexually active and of child-bearing age); VIII. Inability to comply with either the requirements of informed consent or the treatment protocol; IX. Any history of renal disease/impairment, Parkinson’s disease, restless legs syndrome or other movement disorders.
Outcome results
None listed