Ebselen as an add-on Treatment in Hypo/Mania

Study Overview
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Brief Summary
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This study evaluates the effect of a 'lithium like' drug called ebselen (SP-1005) versus placebo as an 'add on' treatment to help stabilise hypo/manic symptoms in bipolar disorder. Half of the participants will receive ebselen and the other half placebo. The trial, will last a total of four weeks.

Detailed Description
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Ebselen, a new drug for mania Bipolar disorder, formerly known as manic depression, is a condition that affects mood, which can swing from one extreme to another. Typically, there will be periods of: Depression - very low mood and energy levels Mania or hypomania (less severe) - very high mood and overactive energy levels A drug called lithium, used to stabilise mood, is an important treatment for bipolar disorder but has a number of problematic side effects, is not well tolerated by patients and requires careful monitoring. To replace lithium with other, safer medicines would have clear advantages. The investigators are interested in an antioxidant medicine(substance that may prevent or delay cell damage) called ebselen which has been shown to work in a similar way as lithium and the investigators are investigating whether it might help improve recovery from manic episodes. The present study aims to see whether ebselen, used as an 'add-on' treatment can help stabilise mood in patients experiencing high mood (hypo/mania). Sixty patients experiencing hypo/mania will be given in a randomised order (similar to tossing a coin) either ebselen or placebo (dummy) in addition to their usual medication for three weeks after which the add-on treatment will be stopped. A final follow up visit will take place one week after the study medication has been stopped. Participants can be in or outpatients and mood will be monitored with questionnaires and interviews. Activity will also be monitored with the use of an actiwatch (similar to a wrist watch) which will be worn continuously throughout the study. A single blood sample will be optional and occur after the first week of treatment to check plasma levels of ebselen and inflammatory markers. A positive outcome in this trial will be followed by longer term studies of ebselen in bipolar disorder.

Official Title
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A Randomised, Parallel Group, Double Blind, Placebo Controlled, Add on Clinical Trial to Investigate Whether the Lithium Mimetic, Ebselen, Can Reduce Symptoms of Hypomania and Mania in Bipolar Patients

Conditions
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Bipolar Disorder, Bipolar Disorder, Manic

Intervention / Treatment
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* Drug: Ebselen
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the trial. Male or Female, aged 18-70 years Diagnosed with bipolar disorder, screened using the Structured Clinical Interview for DSM-5 (SCID) to meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Manic or Hypomanic Episode. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial In the Investigator's opinion, is able and willing to comply with all trial requirements. Willing to allow clinical care team (including General Practitioner (GP)) to be made aware of trial participation. The Clinical team treating the patient are in agreement. Exclusion Criteria: Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. Known significant renal or hepatic impairment. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial. Participants who have participated in another research trial involving an investigational product in the past 12 weeks. Clinically significant illicit substance or alcohol misuse where dependence criteria are satisfied. Taking lithium. Previous randomisation to this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ebselen<br>Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks | Drug: Ebselen<br>* Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.<br>* Other names: Harmokisane;|
| Placebo Comparator: Placebo<br>Three Placebo capsules each containing 200mg taken orally twice a day for 3 weeks | Drug: Placebo oral capsule<br>* Placebo is identical in appearance to the ebselen capsules<br>* Other names: Dummy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Young Mania Rating Scale (YMRS) | Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60. | Change between groups, every week, up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale | Improvement due to treatment between groups. Very much improved to very much worse. | Change between groups, every week, up to 4 weeks | 
| Change in Altman Self Rating Mania Scale (ASRM) | Difference in the 5 item self-rated ASRM between groups.Total score 0-20. | Change between groups, 3 x weekly, up to 4 weeks | 
| Change in Hamilton Rating Scale for Depression (HAM-D) | Difference in the 17 item Clinician-rated HAM-D between groups. Total score 0-52. | Change between groups, every week, up to 4 weeks | 
| Change in Quick Inventory of Depressive Symptomology-Self Rating 16 (QIDS-SR-16) | Difference in the 16 item self-rated QIDS-SR-16 between groups. Total score 0-42. | Change between groups, 3 x weekly, up to 4 weeks | 
| Change in Actigraphy | To compare the effect of ebselen versus placebo on motor behaviour and the sleep-wake cycle | Change in activity between groups, each 24 hours, up to 4 weeks | 
| Change in Leeds Sleep Evaluation Questionnaire (LSEQ) | Difference in the 4 self-rated sleep domains (10 visual analogue scales) between groups. | Change between groups, every week, up to 4 weeks | 
| Levels of markers of inflammation in Plasma sample | To compare the effect of ebselen, versus placebo, on markers of inflammation including C-Reactive Protein and antibodies to common infectious agents such as human herpesviruses and Toxoplasma gondii | Once at week 1 visit | 
| Ebselen levels in Plasma sample | To assess ebselen levels in plasma | Once at week 1 visit | 
| Adverse Events reported | Self-rated Side Effects Questionnaire | Every week, up to 4 weeks | 
| Change in Concomitant medication recorded | To assess the overall use of concomitant medication during the trial period | Change between groups, every week, up to 4 weeks | 
| Compliance assessment | capsule count and records checked | Change between groups, every week, up to 3 weeks |