Bipolar Disorder, Bipolar Disorder, Manic
Conditions
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.
Interventions
DRUGEbselen
Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.
DRUGPlacebo oral capsule
Placebo is identical in appearance to the ebselen capsules
Sponsors
Stanley Medical Research Institute
Sound Pharmaceuticals, Incorporated
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Actigraphy | 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 |
| Adverse Events reported | Every week, up to 4 weeks | Self-rated Side Effects Questionnaire |
| Change in Concomitant medication recorded | Change between groups, every week, up to 4 weeks | To assess the overall use of concomitant medication during the trial period |
| Compliance assessment | Change between groups, every week, up to 3 weeks | capsule count and records checked |
| Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale | 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) | 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) | 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) | 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 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 sample | 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 | Once at week 1 visit | To assess ebselen levels in plasma |
Other
| Measure | Time frame | Description |
|---|---|---|
| Public Participant Involvement (PPI) feedback questionnaire | Once, at week 4 | PPI questionnaire |
| Researcher and participant blinding questionnaire to determine treatment concealment | Once, at week 4 | Researcher and participant blinding questionnaire |
| Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS) | Once, at week 4 | To assess whether researchers and participants could guess the assigned randomised arm |
Countries
United Kingdom
Outcome results
None listed