Ebselen as an add-on Treatment in Hypo/Mania

Bipolar Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03013400
• Other study ID #: 172518
• Secondary ID: 2015-000323-86
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2017
• Est. completion date: July 9, 2019

Study information

• Verified date: November 2017
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 9, 2019
• Est. primary completion date: July 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bipolar Disorder
• Bipolar Disorder, Manic
• Disease

Intervention

Drug:
• Ebselen
Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.
• Placebo oral capsule
Placebo is identical in appearance to the ebselen capsules

Locations

Country	Name	City	State
United Kingdom	Neurosciences Building, Dept. Psychiatry, Warneford Hospital	Oxford	Oxfordshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	Sound Pharmaceuticals, Incorporated, Stanley Medical Research Institute

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

Masaki C, Sharpley AL, Cooper CM, Godlewska BR, Singh N, Vasudevan SR, Harmer CJ, Churchill GC, Sharp T, Rogers RD, Cowen PJ. Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing. Psychopharmacology (Berl). 2016 Jul;233(14):2655-61. doi: 10.1007/s00213-016-4319-5. Epub 2016 Jun 2. — View Citation

Masaki C, Sharpley AL, Godlewska BR, Berrington A, Hashimoto T, Singh N, Vasudevan SR, Emir UE, Churchill GC, Cowen PJ. Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla. Psychopharmacology (Berl). 2016 Mar;233(6):1097-104. doi: 10.1007/s00213-015-4189-2. Epub 2016 Jan 12. — View Citation

Singh N, Halliday AC, Thomas JM, Kuznetsova OV, Baldwin R, Woon EC, Aley PK, Antoniadou I, Sharp T, Vasudevan SR, Churchill GC. A safe lithium mimetic for bipolar disorder. Nat Commun. 2013;4:1332. doi: 10.1038/ncomms2320. — View Citation

Singh N, Sharpley AL, Emir UE, Masaki C, Herzallah MM, Gluck MA, Sharp T, Harmer CJ, Vasudevan SR, Cowen PJ, Churchill GC. Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans. Neuropsychopharmacology. 2016 Jun;41(7):1768-78. doi: 10.1038/npp.2015.343. Epub 2015 Nov 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Researcher and participant blinding questionnaire to determine treatment concealment	Researcher and participant blinding questionnaire	Once, at week 4
Other	Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS)	To assess whether researchers and participants could guess the assigned randomised arm	Once, at week 4
Other	Public Participant Involvement (PPI) feedback questionnaire	PPI questionnaire	Once, at week 4
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Ebselen levels in Plasma sample	To assess ebselen levels in plasma	Once at week 1 visit
Secondary	Adverse Events reported	Self-rated Side Effects Questionnaire	Every week, up to 4 weeks
Secondary	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
Secondary	Compliance assessment	capsule count and records checked	Change between groups, every week, up to 3 weeks