IMPase in Treatment-resistant Depression

• Status: Recruiting
• Trial end date: 2023-05-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborator: Medical Research Council
• Treatments: Ebselen

Criteria

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 Practictioner (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.