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Ebselen as an add-on Treatment in Hypo/Mania

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2017 by University of Oxford
Sponsor:
Collaborators:
Stanley Medical Research Institute
Sound Pharmaceuticals, Incorporated
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT03013400
First received: December 9, 2016
Last updated: January 10, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Bipolar Disorder
Bipolar Disorder, Manic
Drug: Ebselen
Drug: Placebo Oral Capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Change in Young Mania Rating Scale (YMRS) [ Time Frame: Change between groups, every week, up to 4 weeks ] [ Designated as safety issue: No ]
    Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60.


Secondary Outcome Measures:
  • Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale [ Time Frame: Change between groups, every week, up to 4 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To assess ebselen levels in plasma

  • Adverse Events reported [ Time Frame: Every week, up to 4 weeks ] [ Designated as safety issue: No ]
    Self-rated Side Effects Questionnaire

  • Change in Concomitant medication recorded [ Time Frame: Change between groups, every week, up to 4 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    capsule count and records checked


Other Outcome Measures:
  • Researcher and participant blinding questionnaire to determine treatment concealment [ Time Frame: Once, at week 4 ] [ Designated as safety issue: No ]
    Researcher and participant blinding questionnaire

  • Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS) [ Time Frame: Once, at week 4 ] [ Designated as safety issue: No ]
    To assess whether researchers and participants could guess the assigned randomised arm

  • Public Participant Involvement (PPI) feedback questionnaire [ Time Frame: Once, at week 4 ] [ Designated as safety issue: No ]
    PPI questionnaire


Estimated Enrollment: 60
Study Start Date: June 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ebselen
Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks
Drug: Ebselen
Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.
Other Names:
  • SPI-1005
  • PZ-51
  • Ebselene
  • Ebselenum
  • Ebseleno
  • Harmokisane
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03013400

Contacts
Contact: Ann L Sharpley, BSc.,PhD 01865618321 ann.sharpley@psych.ox.ac.uk
Contact: Philip J Cowen, MBBS, MD 01865618311 phil.cowen@psych.ox.ac.uk

Sponsors and Collaborators
University of Oxford
Stanley Medical Research Institute
Sound Pharmaceuticals, Incorporated
Investigators
Principal Investigator: Philip J Cowen, MBBS, MD University of Oxford
  More Information

Publications:
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03013400     History of Changes
Other Study ID Numbers: 172518  2015-000323-86 
Study First Received: December 9, 2016
Last Updated: January 10, 2017
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Ebselen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Neuroprotective Agents

ClinicalTrials.gov processed this record on January 17, 2017