A study to look at Ketamine as an additional treatment for people with depressio

Phase 1

Conditions: Major Depression
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Registration Number: EUCTR2019-003109-92-IE

Lead Sponsor: Trinity College Dublin

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 104

Inclusion Criteria

Participants may be male or female, aged =18 years, and from a variety of geographical (within Ireland) and socioeconomic backgrounds. To be eligible for inclusion, each participant must meet each of the following criteria at screening (Visit 0) and continue to fulfil these criteria at baseline before the first ketamine/midazolam infusion (Visit 1).

1. Participants must be voluntary admissions and able and willing to give written informed consent and comply with the requirements of this study protocol.
2. Admitted to hospital and diagnosed with major depressive disorder or bipolar disorder (current episode depression), confirmed by the Mini International Neuropsychiatric Interview (MINI); and have a Montgomery-Åsberg Rating Scale for Depression (MADRS) score =20 at screening and start of the first infusion.
3. Female patients of child-bearing potential and male patients whose partner is of child-bearing potential must be willing to ensure that they or their partner use two contraception methods, including a barrier method, during the randomised treatment phase and for 12 weeks thereafter.
4. Female patients' plasma pregnancy test performed at the screening visit must be negative.
5. Patients have clinically acceptable laboratory and ECG findings during the current admission prior to the first infusion session.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 78
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion Criteria

Patients are excluded from the study if any of the following criteria are met at Screening (Visit 0) or at baseline before the first infusion session (Visit 1):

1. Current involuntary admission
2. Patients unable to provide written informed consent
3. Patients who have participated in another ketamine study or received any other investigational agent within the past 12 months
4. Medical condition rendering unfit for ketamine or midazolam (Ketamine is contraindicated, as per Summary of Product Characteristics, in persons in whom an elevation of blood pressure would constitute a serious hazard. Ketamine should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, C.V.A. or cerebral trauma or if there is hypersensitivity to the active substance. Contraindications to midazolam include known hypersensitivity to benzodiazepines, severe respiratory failure or acute respiratory depression. Bradycardia is a known adverse effect of midazolam and ketamine. Therefore, patients with pre-existing bradycardia will be excluded.)
5. Currently taking any of the following medications which are contraindicated during the randomised treatment period as they may alter the pharmacokinetics of ketamine. Additionally, the medication theophylline is contraindicated as concomitant use of ketamine and theophylline may significantly reduce the seizure threshold with reports of unpredictable extensor-type seizures.

Contraindicated medications:
Ketoconazole
Voriconazole
Itraconazole
Fluconazole
Erythromycin
Telithromycin
Clarithromycin
Saquinavir
Nefazodone
Diltiazem
Verapamil
Theophylline

6. Active suicidal intention (score of 6 on item 10 (Suicidal Thoughts) in the MADRS)
7. Confirmed diagnosis of dementia
8. Lifetime history of schizophrenia or schizoaffective disorder; active anorexia nervosa or bulimia nervosa in the past 12 months; alcohol or other substance use disorder (with the exception of nicotine) in the previous six months; any DSM-5 disorder other than a major depressive episode (unipolar or bipolar) as the primary presenting problem
9. ECT administered within the last two months
10. Pregnancy or inability to confirm use of adequate contraception during the trial
11. Breastfeeding women