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Ebselen as an add-on Treatment in Hypo/Mania

Phase 2
Completed
Conditions
Bipolar Disorder
Bipolar Disorder, Manic
Interventions
Drug: Placebo oral capsule
Registration Number
NCT03013400
Lead Sponsor
University of Oxford
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo oral capsuleThree Placebo capsules each containing 200mg taken orally twice a day for 3 weeks
EbselenEbselenThree Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks
Primary Outcome Measures
NameTimeMethod
Change in Young Mania Rating Scale (YMRS)Change between groups, every week, up to 4 weeks

Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60.

Secondary Outcome Measures
NameTimeMethod
Change in Clinical Global Impressions Bipolar (CGI-BP) mania scaleChange between groups, every week, up to 4 weeks

Improvement due to treatment between groups. Very much improved to very much worse.

Change in Quick Inventory of Depressive Symptomology-Self Rating 16 (QIDS-SR-16)Change between groups, 3 x weekly, up to 4 weeks

Difference in the 16 item self-rated QIDS-SR-16 between groups. Total score 0-42.

Ebselen levels in Plasma sampleOnce at week 1 visit

To assess ebselen levels in plasma

Change in Concomitant medication recordedChange between groups, every week, up to 4 weeks

To assess the overall use of concomitant medication during the trial period

Change in Hamilton Rating Scale for Depression (HAM-D)Change between groups, every week, up to 4 weeks

Difference in the 17 item Clinician-rated HAM-D between groups. Total score 0-52.

Compliance assessmentChange between groups, every week, up to 3 weeks

capsule count and records checked

Change in Altman Self Rating Mania Scale (ASRM)Change between groups, 3 x weekly, up to 4 weeks

Difference in the 5 item self-rated ASRM between groups.Total score 0-20.

Change in ActigraphyChange in activity between groups, each 24 hours, up to 4 weeks

To compare the effect of ebselen versus placebo on motor behaviour and the sleep-wake cycle

Change in Leeds Sleep Evaluation Questionnaire (LSEQ)Change between groups, every week, up to 4 weeks

Difference in the 4 self-rated sleep domains (10 visual analogue scales) between groups.

Levels of markers of inflammation in Plasma sampleOnce at week 1 visit

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

Adverse Events reportedEvery week, up to 4 weeks

Self-rated Side Effects Questionnaire

Trial Locations

Locations (1)

Neurosciences Building, Dept. Psychiatry, Warneford Hospital

🇬🇧

Oxford, Oxfordshire, United Kingdom

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