Bipolar DisorderPhase 2NCT03013400
Ebselen as an add-on Treatment in Hypo/Mania
A Phase 2 study testing Ebselen in people with Bipolar Disorder and Bipolar Disorder, Manic, run by University of Oxford at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bipolar Disorder, Bipolar Disorder, Manic
- What is being tested?
- Ebselen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2017to 9 Jul 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Neurosciences Building, Dept. Psychiatry, Warneford Hospital
Oxford, Oxfordshire, OX37JX
About this study
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
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.
Read the 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.
- Conditions
- Bipolar Disorder, Bipolar Disorder, Manic
- Being tested
- Ebselen, Placebo oral capsule
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EbselenDrug
Also called SPI-1005, PZ-51, Ebselene, Ebselenum
Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.
Placebo oral capsuleDrug
Also called Dummy
Placebo is identical in appearance to the ebselen capsules
| Study group | Role | What they receive |
|---|---|---|
| Ebselen | Active comparator | Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks Receives: Drug: Ebselen |
| Placebo | Placebo comparator | Three Placebo capsules each containing 200mg taken orally twice a day for 3 weeks Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Young Mania Rating Scale (YMRS)
Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60.
Measured: Change between groups, every week, up to 4 weeks
Secondary outcomes (11)
Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale
Improvement due to treatment between groups. Very much improved to very much worse.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: Once at week 1 visit
Ebselen levels in Plasma sample
To assess ebselen levels in plasma
Measured: Once at week 1 visit
Adverse Events reported
Self-rated Side Effects Questionnaire
Measured: Every week, up to 4 weeks
Change in Concomitant medication recorded
To assess the overall use of concomitant medication during the trial period
Measured: Change between groups, every week, up to 4 weeks
Compliance assessment
capsule count and records checked
Measured: Change between groups, every week, up to 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2017 (estimated)
- Study start1 Oct 2017
- Primary completion9 Jul 2019
- Study completion9 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute, Sound Pharmaceuticals, Incorporated
- Responsible party
- Sponsor
- Investigators
- Philip J Cowen, MBBS, MD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03013400
- Sponsor's protocol ID
- 172518
- Other IDs
- 2015-000323-86, 2015
- Status last verified
- Nov 2017
- First submitted
- 9 Dec 2016
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 27256357Masaki 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.
PubMed 26758281Singh 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.
PubMed 26593266Singh 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.
PubMed 23299882Sharpley AL, Williams C, Holder AA, Godlewska BR, Singh N, Shanyinde M, MacDonald O, Cowen PJ. A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania. Psychopharmacology (Berl). 2020 Dec;237(12):3773-3782. doi: 10.1007/s00213-020-05654-1. Epub 2020 Sep 9.
PubMed 32909076Garland M, Hryckowian AJ, Tholen M, Bender KO, Van Treuren WW, Loscher S, Sonnenburg JL, Bogyo M. The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI. Cell Rep Med. 2020 Apr 21;1(1):100005. doi: 10.1016/j.xcrm.2020.100005.
PubMed 32483557
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03013400
- Acronym / sponsor ID
- 172518
- Conditions
- Bipolar Disorder, Bipolar Disorder, Manic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute, Sound Pharmaceuticals, Incorporated
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 9 Jul 2019 (actual)
- Study completion
- 9 Jul 2019 (actual)
- First posted
- 6 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ebselen | Active comparator | Drug: EbselenThree Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks |
| Placebo | Placebo comparator | Drug: Placebo oral capsuleThree Placebo capsules each containing 200mg taken orally twice a day for 3 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EbselenAlso: SPI-1005, PZ-51, Ebselene, EbselenumEbselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor. | Drug | Ebselen |
| Placebo oral capsuleAlso: DummyPlacebo is identical in appearance to the ebselen capsules | Drug | Placebo |
Primary outcome
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.
11 secondary outcomes
Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale
Time frame: Change between groups, every week, up to 4 weeks
Change in Altman Self Rating Mania Scale (ASRM)
Time frame: Change between groups, 3 x weekly, up to 4 weeks
Change in Hamilton Rating Scale for Depression (HAM-D)
Time frame: Change between groups, every week, up to 4 weeks
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
Change in Actigraphy
Time frame: Change in activity between groups, each 24 hours, up to 4 weeks
Change in Leeds Sleep Evaluation Questionnaire (LSEQ)
Time frame: Change between groups, every week, up to 4 weeks
Levels of markers of inflammation in Plasma sample
Time frame: Once at week 1 visit
Ebselen levels in Plasma sample
Time frame: Once at week 1 visit
Adverse Events reported
Time frame: Every week, up to 4 weeks
Change in Concomitant medication recorded
Time frame: Change between groups, every week, up to 4 weeks
Compliance assessment
Time frame: Change between groups, every week, up to 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Background: PubMed 27256357Masaki 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.
- Background: PubMed 26758281Masaki 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.
- Background: PubMed 26593266Singh 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.
- Background: PubMed 23299882Singh 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.
- Derived from this study: PubMed 32909076Sharpley AL, Williams C, Holder AA, Godlewska BR, Singh N, Shanyinde M, MacDonald O, Cowen PJ. A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania. Psychopharmacology (Berl). 2020 Dec;237(12):3773-3782. doi: 10.1007/s00213-020-05654-1. Epub 2020 Sep 9.
- Derived from this study: PubMed 32483557Garland M, Hryckowian AJ, Tholen M, Bender KO, Van Treuren WW, Loscher S, Sonnenburg JL, Bogyo M. The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI. Cell Rep Med. 2020 Apr 21;1(1):100005. doi: 10.1016/j.xcrm.2020.100005.
- Individual participant dataSharing planned: Undecided
Related trials for Bipolar Disorder
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip J Cowen, MBBS, MD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ebselen in people with Bipolar Disorder and Bipolar Disorder, Manic, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Young Mania Rating Scale (YMRS) (time frame: Change between groups, every week, up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03013400, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.