E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
To conduct a randomised controlled patient- and rater-blinded pilot trial of twice weekly ketamine vs. midazolam as an adjunctive therapy interleaved with ECT in the treatment of a major depressive episode. Assess feasibility of a future definitive trial. |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability of repeated twice-weekly infusions of ketamine vs. midazolam in this depressed population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• ≥18 years old • Able to provide informed consent • Voluntary admission for treatment of an acute depressive episode • Meet DSM-V criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression) • Montgomery Asberg Depression Rating Scale 10 item version (MADRS) score of ≥20 • Referred for treatment with ECT • Sufficiently physically healthy to receive ketamine/midazolam and ECT
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E.4 | Principal exclusion criteria |
• Inability to provide informed consent • Current involuntary admission • History of Axis 1 diagnosis other than major depression • Medical condition rendering unfit for ketamine/midazolam or ECT • Active suicidal intention • Presence of major neurological or organic brain disorder • Alcohol/substance dependence in previous six-months • Pregnancy or inability to confirm use of adequate contraception during the trial • Breastfeeding women
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E.5 End points |
E.5.1 | Primary end point(s) |
This pilot trial is not designed to assess efficacy. Rather, a 95% confidence interval for the difference between MADRS scores between ketamine and midazolam groups, at various timepoints, will be obtained, to inform a future definitive trial. We will measure these MADRS scores at baseline, during after infusions, one week after the final infusion and at 6 and 12 weeks post final infusion. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint of this polit trial is successful completion of the trial protocol. Process outcomes such as recruitment and retention rates are the primary focus. Recruitment will cease once 24 participants have been randomised. We will measure these MADRS scores at baseline, during after infusions, one week after the final infusion and at 6 and 12 weeks post final infusion. |
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E.5.2 | Secondary end point(s) |
Clinical outcomes are secondary. The primary clinical outcome is a decrease in depressive symptoms, measured using the objectively-rated 10-item Montgomery Asberg Rating Scale (MADRS). 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 MADRS 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Standard criteria for depression severity, treatment response, remission and relapse will be used in a three-month follow-up schedule which involves the MADRS and other instruments at weeks 6 and 12 post final infusion |
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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 |
The is primarily a pilot trial to assess feasibility of a future definite trial |
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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 | Yes |
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 |
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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
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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 |