Depressive Disorder, Treatment-Resistant Clinical Trial
— OxIMPOfficial title:
Does the IMPase Inhibitor, Ebselen, Affect Emotional Processing and Brain Myo-inositol in Treatment-resistant Depression?
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.
Status | Recruiting |
Enrollment | 50 |
Est. completion date | May 31, 2024 |
Est. primary completion date | May 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: - 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); - Sexual abstinence. [Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), and spermicides only are not acceptable methods of contraception.] - Male participants must not donate sperm. - Participants taking non-prescription/prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety - Willing to refrain from drinking alcohol for the duration of the study Exclusion Criteria: - 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. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Neurosciences Building, Dept. Psychiatry, Warneford Hospital | Oxford | Oxfordshire |
Lead Sponsor | Collaborator |
---|---|
University of Oxford | Medical Research Council, Sound Pharmaceuticals, Incorporated |
United Kingdom,
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. — View Citation
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
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. — 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
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | 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 | Change in accuracy in the Emotional Categorisation Task | Difference in Emotional Categorisation Task (ECAT): accuracy to classify positive and negative descriptor words | Change between groups from baseline to day 7 | |
Secondary | Change in reaction time in the Emotional Categorisation Task (ECAT) | Differences in reaction time to classify positive and negative descriptor words | Change between groups from baseline to day 7 | |
Secondary | Change on Facial Dot Probe Task (FDOT) | Differences in Vigilance scores derived from reaction time | Change between groups from baseline to day 7 | |
Secondary | Change on Emotional Recall Task (EREC) | Differences in number of words correctly recalled (hits) and number of words incorrectly recalled (false alarms). | Change between groups from baseline to day 7 | |
Secondary | Change on Emotional Recognition Memory Task (EMEM) | Difference in Emotional Recognition Memory Task (EMEM): accuracy and reaction time to correctly recognise positive and negative words (hits), and number of incorrectly recognised words (false alarms) | Change between groups from baseline to day 7 | |
Secondary | Change on brain inositol levels | Difference in levels of inositol as determined by magnetic resonance spectroscopy (MRS) | Change between groups from baseline to day 7 | |
Secondary | Change on glutamate levels | Difference in levels of glutamate as determined by MRS | Change between groups from baseline to day 7 | |
Secondary | Change on glutamine levels | Difference in levels of glutamine as determined by MRS | Change between groups from baseline to day 7 | |
Secondary | Change on choline levels | Difference in levels of choline as determined by MRS | Change between groups from baseline to day 7 | |
Secondary | Change in Montgomery-Åsberg Depression Rating scale (MADRS) | Difference in the 10-item MADRS between groups. Total score 0-60. | Change between groups from baseline to day 7 | |
Secondary | Change in the Quick Inventory of Depressive Symptomatology-Self report (QIDS-SR) | Difference in 16 item self-rated QIDS-SR between groups. Total score 0-42. | Change between groups from baseline to day 7 | |
Secondary | Change in Generalised Anxiety Disorder Assessment -7 (GAD-7) | Difference in the 7 item self-rated GAD-7 between groups. Total score 0-21 | Change between groups from baseline to day 7 |
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