E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major depressive disorder (MDD) |
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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 |
This is a clinical study of the downstream mechanism of action of SSRI treatment for MDD. Primary research questions (outcomes): • Does SSRI for MDD reduce serotonin 1B (5-HT1B) receptor binding in the raphe nuclei and increase 5-HT1B receptor binding in serotonin projection areas? • Is this putative change in 5-HT1B receptor binding related to change in MDD symptom rating scores or side effects?
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E.2.2 | Secondary objectives of the trial |
Secondary research questions: • Does SSRI for MDD alter p11 concentration in leucocytes in peripheral blood? • Does a potential change in p11 concentration correlate with 5-HT1B receptor binding in relevant brain regions? • Does change in p11 correlate with change in MDD symptom rating scores? • Is brain activity to fearful versus happy faces reduced in MDD patients who are to respond to SSRI treatment? • Is reward reversal learning impaired in MDD patients? Do the test scores correlate with 5-HT1B receptor binding or brain activity in the striatum? • Is a change in brain activity related to change in 5-HT1B receptor binding or blood p11? • Does a change in brain activity correlate with change in MDD symptom rating scores? • Is the physical activity pattern changed after SSRI? Is any such change related to 5-HT1B receptor binding, brain activity, p11 leucocyte concentration or MDD treatment response?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• age 20-80 years • ongoing major depressive episode according to M.I.N.I. interview • healthy, apart from MDD, according to MRI, clinical interview, physical examination, blood tests (Hb, ASAT, ALAT, GT, Na, K, creatinine, calcium, albumin, TSH, glucose). • MADRS>20
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E.4 | Principal exclusion criteria |
• ongoing pharmacological treatment (wash out-time one month, drugs not used for MDD treatment and without serotonergic effect may be allowed at the discretion of the PI) • bipolar disorder • psychotic syndrome • alcohol/drug dependence • organic central nervous system disorder • patient who is not suitable for MRI (claustrophobia, MRI incompatible metal implants) • pregnancy. • Allergy or hypersensitivity to escitalopram • Ongoing treatment with any medication that is known to prolong the QT interval • Ongoing treatment with any monoamine oxidase inhibitor
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is significant change in brain 5-HT1B receptor binding after SSRI treatment for MDD in relation to treatment effect. Based on the previous literature we hypothesize that 5-HT1B receptor binding will be reduced in the raphe nuclei and increased in serotonin projection areas after SSRI. We plan to examine 20 patients, in accordance with a power calculation based on previous examinations of reduced 5-HT1B receptor binding in the raphe nuclei with MDD treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoints will be evaluated after three weeks of SSRI treatments. Antidepressant effect will be evaluated after six weeks´escitalopram treatment. |
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E.5.2 | Secondary end point(s) |
• Change in p11 concentration in leucocytes in peripheral blood after escitalopram treatment • Brain activity to fearful versus happy faces in relation to escitalopram treatment response • Physical activity pattern before treatment in relation to escitalopram treatment response • Correlation between potential change in p11 concentration and 5-HT1B receptor binding in relevant brain regions • Correlation between change in p11 and change in MDD symptom rating scores? • Is reward reversal learning impaired in MDD patients? Do the test scores correlate with 5-HT1B receptor binding or brain activity in the striatum? • Is a change in brain activity related to change in 5-HT1B receptor binding or blood p11? • Does a change in brain activity correlate with change in MDD symptom rating scores? • Is the physical activity pattern changed after SSRI? Is any such change related to 5-HT1B receptor binding, brain activity, p11 leucocyte concentration or MDD treatment response? • Change in neuromelanin accumulation index with escitalopram treatment • Changes in cognitive test performance after escitalopram treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints will be evaluated after three weeks of SSRI treatment. Antidepressant effect will be evaluated after six weeks´escitalopram treatment. |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |