Ebselen as an add-on Treatment in Hypo/Mania

NCT03013400 | Completed Phase 2 DMC

• 2 other identifiers: 1725182015-000323-86
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Disorder; Bipolar Disorder, Manic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale

  Change between groups, every week, up to 4 weeks

• Change in Altman Self Rating Mania Scale (ASRM)

  Change between groups, 3 x weekly, up to 4 weeks

• Change in Hamilton Rating Scale for Depression (HAM-D)

  Change between groups, every week, up to 4 weeks

• Change in Quick Inventory of Depressive Symptomology-Self Rating 16 (QIDS-SR-16)

  Change between groups, 3 x weekly, up to 4 weeks

• Change in Actigraphy

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

Other Outcomes (3)

• Researcher and participant blinding questionnaire to determine treatment concealment

  Once, at week 4

• Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS)

  Once, at week 4

• Public Participant Involvement (PPI) feedback questionnaire

  Once, at week 4

Study Arms (2)

Ebselen

ACTIVE COMPARATOR

Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks

Drug: Ebselen

Placebo

PLACEBO COMPARATOR

Three Placebo capsules each containing 200mg taken orally twice a day for 3 weeks

Drug: Placebo oral capsule

Interventions

Ebselen DRUG

Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.

Also known as: SPI-1005, PZ-51, Ebselene, Ebselenum, Ebseleno, Harmokisane

Ebselen

Placebo oral capsule DRUG

Placebo is identical in appearance to the ebselen capsules

Also known as: Dummy

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Stanley Medical Research Institute: collaborator
• Sound Pharmaceuticals, Incorporated: collaborator

Study Sites (1)

Neurosciences Building, Dept. Psychiatry, Warneford Hospital

Oxford, Oxfordshire, OX37JX, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 27256357 BACKGROUND

• 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.

  PMID: 26758281 BACKGROUND

• 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.

  PMID: 26593266 BACKGROUND

• 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.

  PMID: 23299882 BACKGROUND

• Sharpley 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.

  PMID: 32909076 DERIVED

• Garland 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.

  PMID: 32483557 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

ebselen

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Officials

• Philip J Cowen, MBBS, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2016
• First Posted: January 6, 2017
• Study Start: October 1, 2017
• Primary Completion: July 9, 2019
• Study Completion: July 9, 2019
• Last Updated: September 6, 2019

Record last verified: 2017-11

Locations

GB (1)