Ebselen as an add-on Treatment in Hypo/Mania
|Bipolar Disorder Bipolar Disorder, Manic||Drug: Ebselen Drug: Placebo Oral Capsule||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Change in Young Mania Rating Scale (YMRS) [ Time Frame: Change between groups, every week, up to 4 weeks ]Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60.
- Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale [ Time Frame: Change between groups, every week, up to 4 weeks ]Improvement due to treatment between groups. Very much improved to very much worse.
- Change in Altman Self Rating Mania Scale (ASRM) [ Time Frame: 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 Hamilton Rating Scale for Depression (HAM-D) [ Time Frame: Change between groups, every week, up to 4 weeks ]Difference in the 17 item Clinician-rated HAM-D between groups. Total score 0-52.
- Change in Quick Inventory of Depressive Symptomology-Self Rating 16 (QIDS-SR-16) [ Time Frame: 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.
- Change in Actigraphy [ Time Frame: Change 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) [ Time Frame: 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 sample [ Time Frame: Once 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
- Ebselen levels in Plasma sample [ Time Frame: Once at week 1 visit ]To assess ebselen levels in plasma
- Adverse Events reported [ Time Frame: Every week, up to 4 weeks ]Self-rated Side Effects Questionnaire
- Change in Concomitant medication recorded [ Time Frame: Change between groups, every week, up to 4 weeks ]To assess the overall use of concomitant medication during the trial period
- Compliance assessment [ Time Frame: Change between groups, every week, up to 3 weeks ]capsule count and records checked
- Researcher and participant blinding questionnaire to determine treatment concealment [ Time Frame: Once, at week 4 ]Researcher and participant blinding questionnaire
- Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS) [ Time Frame: Once, at week 4 ]To assess whether researchers and participants could guess the assigned randomised arm
- Public Participant Involvement (PPI) feedback questionnaire [ Time Frame: Once, at week 4 ]PPI questionnaire
|Anticipated Study Start Date:||June 30, 2017|
|Estimated Study Completion Date:||June 2020|
|Estimated Primary Completion Date:||June 2020 (Final data collection date for primary outcome measure)|
Active Comparator: Ebselen
Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks
Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.
Placebo Comparator: Placebo
Three Placebo capsules each containing 200mg taken orally twice a day for 3 weeks
Drug: Placebo Oral Capsule
Placebo is identical in appearance to the ebselen capsules
Other Name: Dummy
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03013400
|Contact: Ann L Sharpley, BSc.,PhDfirstname.lastname@example.org|
|Contact: Philip J Cowen, MBBS, MDemail@example.com|
|Principal Investigator:||Philip J Cowen, MBBS, MD||University of Oxford|