E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this trial is to assess ketamine as an adjunctive therapy in major depression. We hypothesise that ketamine will accelerate the recovery time in those patients who have been admitted to hospital with a depressive episode. |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the safety and tolerability of repeated (x4) infusions of ketamine vs. midazolam in this patient population. 2. To explore the role of ketamine-induced changes in peripheral blood neuroplasticity molecules for: (i) monitoring biological response to ketamine during the first infusion and (ii) for evaluating this biological response in treating depression. 3. To investigate epigenetic modulation of depression/stress-related genes in patients being treated with ketamine.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• ≥18 years old • Hamilton Rating Scale for Depression-24 item version (HRSD-24) score of ≥21 • Voluntary admission for treatment of an acute depressive episode • Meet DSM-IV criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)
|
|
E.4 | Principal exclusion criteria |
• Current involuntary admission • Medical condition rendering unfit for ketamine/midazolam • Active suicidal intention • Dementia • History of Axis 1 diagnosis other than major depression • Electroconvulsive Therapy (ECT) administered within the last two months • Alcohol/substance dependence in previous six-months • Pregnancy or inability to confirm use of adequate contraception during the trial
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The focus of a pilot trial’s outcomes is on trial process with assessment of the primary clinical outcome being secondary because the pilot itself is not designed to measure efficacy. Process outcomes that will inform a future definitive trial incluse the following: • recruitment methods and rate • willingness of participants to be randomised • willingness of participants to complete assessments • randomisation • success of blinding • ability to administer a course of ketamine infusions • medical safety and acceptability of ketamine infusions • rates of adverse dissociative and psychiatric events • adherence to allocated treatment • adherence to follow up • reasons for drop-out from treatment • reasons for drop-out from follow-up • establish a 95% confidence interval for the differences between the ketamine and midazolam groups during the 4-week treatment phase to help with power calculations for a future definitive trial
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint of this pilot trial is successful completion of the trial protocol. Process outcomes such as recruitment and retention rates are the primary focus. Recruitment will cease when 40 participants have been randomised. |
|
E.5.2 | Secondary end point(s) |
Clinical outcomes are secondary. The primary clinical outcome is change in score of the objectively-rated 24-item Hamilton Rating Scale for Depression (HRSD-24). Standard criteria for depression severity, treatment response, remission and relapse will be used (please see definitions in "assessments") in a three-month follow-up schedule which involves the HRSD-24 and other instruments at weeks 6 and 12 post-final infusion. Safety and tolerability outcomes consist of psychotomimetic, dissociative, cognitive and physical health effects of repeated ketamine infusions, measured before, during and after infusions using a range of validated instruments.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Participants will be assessed at baseline (on admission to hospital), and on a weekly basis using the primary clinical outcome, the HRSD-24. Those who are eligible for the study, will be invited to be randomised to a four-week course of once-weekly ketamine vs. midazolam infusions. The HRSD-24 will be assessed at each infusion session and at weeks 6 and 12. Cognitive outcomes will be assessed following randomization and repeated at week 12. Tolerability outcomes e.g. the Young Mania Rating Scale, Brief Psychiatric Rating Scale etc, will be assessed before, during and after each infusion session. In total, follow-up will take place over three months.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
This is primarily a pilot trial to assess the feasibility of the proposed protocol. |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |