IMPase in Treatment-resistant Depression

NCT05117710 | Unknown Phase 1

• 2 other identifiers: 27621120/SC/0151
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This experimental medicine study will examine the effects of a brief period (seven days) of 'add on' ebselen (SPI-105) treatment in patients with resistant depression to see if ebselen produces changes in emotional responses consistent with a potential clinical antidepressant effect. The investigators will also seek to confirm ebselen's mode of action on IMPase by measuring changes in a brain chemical called inositol, using a magnetic imaging method. Half of the participants will receive ebselen and the other half placebo.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Treatment Resistant Depression; Ebselen

Outcome Measures

Primary Outcomes (3)

• Change in positive and negative facial expression recognition task

  Difference in accuracy to recognise computer-based positive and negative facial expressions (anger, disgust, fear, happy, sad, surprise)

  Change between groups from baseline to day 7

• Change in misclassifications on emotional processing task

  Differences in misclassifications (number of responses to each facial expression category incorrectly classified as another facial expression category).

  Change between groups from baseline to day 7

• Change in reaction time on emotional processing task

  Differences in reaction time to recognise facial expressions

  Change between groups from baseline to day 7

Secondary Outcomes (12)

• Change in accuracy in the Emotional Categorisation Task

  Change between groups from baseline to day 7

• Change in reaction time in the Emotional Categorisation Task (ECAT)

  Change between groups from baseline to day 7

• Change on Facial Dot Probe Task (FDOT)

  Change between groups from baseline to day 7

• Change on Emotional Recall Task (EREC)

  Change between groups from baseline to day 7

• Change on Emotional Recognition Memory Task (EMEM)

  Change between groups from baseline to day 7

Study Arms (2)

Ebselen

ACTIVE COMPARATOR

The intervention will be 7-10 days administration of ebselen 600 mg twice daily taken orally. Ebselen has been manufactured to Good Manufacturing Practice (GMP) standards and will be provided by Sound Pharmaceuticals Inc. in 200 mg capsules.

Drug: Ebselen

Placebo

PLACEBO COMPARATOR

The intervention will be 7-10 days administration of placebo 600 mg twice daily taken orally.Identical placebo capsules have been manufactured and formulated in the same facilities as the active treatment.

Drug: Placebo

Interventions

Ebselen DRUG

Ebselen is an organoselenium compound, developed originally as an antioxidant for use in neuroprotection, post-stroke. Ebselen is a bioavailable and brain penetrant inhibitor of inositol monophosphatase (IMPase) (Ki ≈ 1 μM).

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

Ebselen

Placebo DRUG

Matched placebo 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:

• Willing and able to give informed consent for participation in the study;
• Sufficiently fluent English to understand and complete the tasks;
• Registered with a General Practitioner (GP) and consents to GP being informed of participation in the study;
• Participants need to meet a number of concurrent clinical criteria:
• Current criteria for Major Depressive Disorder as determined by the Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5);
• Inadequate response to at least one adequate course of antidepressant therapy given at a therapeutic dose for at least four weeks in the current episode of depression.
• Minimum score on the 17-item Hamilton Depression Rating Scale (HAM-D) of at least 14;
• Currently taking a licensed antidepressant at a therapeutic dose for at least four weeks
• Pre-menopausal women and male participants engaging in sex with a risk of pregnancy must agree to use a highly effective method of contraception from Screening Visit until 30 days after receiving the study medication treatment. Acceptable methods of contraception include:
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal;
• Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable;
• Intrauterine device (IUD);
• Intrauterine hormone-releasing system (IUS);
• Bilateral tubal occlusion;
• Vasectomy (or vasectomised partner);

You may not qualify if:

• History of /or current DSM-5 bipolar disorder, schizophrenia or emotionally unstable personality disorder;
• Participants who fulfil current criteria for other comorbid disorders may still be entered into the study, if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality;
• Participants who have failed to respond to standard pharmacological augmentation treatments for depression (lithium and atypical antipsychotic drugs);
• Clinically significant risk of suicide;
• Participants undergoing or who have undergone electroconvulsive therapy for the treatment of the current episode of depression;
• History of significant alcohol/substance misuse or dependence over the past 6 months;
• History of, or current general medical conditions that in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study;
• Current pregnancy (as determined by urine pregnancy test taken during the Screening Visit and the Research Visit One), breastfeeding, or planning a pregnancy during the course of the study;
• Participants with Body Mass Index (BMI - kg/m2) outside the 18-36 range at Screening Visit;
• Participants with severe claustrophobia;
• Participants who are contraindicated for MRI;
• Previous participation in a study using the same, or similar, emotional processing tasks in the last three months;
• Previous participation in a study involving the use of an interventional medication within the last three months;
• Participant with planned medical treatment within the study period that might interfere with the study procedures;
• Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.

Sponsors & Collaborators

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

Study Sites (1)

Neurosciences Building, Dept. Psychiatry, Warneford Hospital

Oxford, Oxfordshire, OX37JX, United Kingdom

RECRUITING

Related Publications (5)

• 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 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

• 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

• Kil J, Lobarinas E, Spankovich C, Griffiths SK, Antonelli PJ, Lynch ED, Le Prell CG. Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2017 Sep 2;390(10098):969-979. doi: 10.1016/S0140-6736(17)31791-9. Epub 2017 Jul 14.

  PMID: 28716314 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

ebselen

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Philip J Cowen, MBBS, MD

  Dept. Psychiatry, University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philip J Cowen, MBBS,MD

CONTACT

+44 1865 618311; phil.cowen@psych.ox.ac.uk

Beata Godlewska, MBBS,MD

CONTACT

+44 1865 618309; beata.godlewska@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple masking
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel-arm, double-blind, randomised, placebo-controlled

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: November 11, 2021
• Study Start: April 22, 2021
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: July 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)