E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
30-40% of depressed patients do not respond to the first course of drug treatment chosen. Over 50% of nonresponders to the first treatment also do not respond to a second, different treatment . Of those who do respond to the initial antidepressant, up to 50% do not reach full remission but rather display residual symptoms. Therefore, treatment optimization strategies should be considered at critical decision points early in the treatment progress to avoid prolonged treatment-resistant courses. |
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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 evaluate the efficacy and safety of lithium augmentation in escitalopram treated patients with a major depressive episode.
Primary endpoint: time to remission (HAMD-17≤7)
Primary endpoint is the score on the Hamilton Depression Rating Scale for Efficacy of antidepressant therapy, safety and side effect monitoring with FISER/GRESB, PRISE and adverse event monitoring. |
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E.2.2 | Secondary objectives of the trial |
To identify those patients who are most responsive to this treatment strategy, we search for genetic and clinical predictors of response to a lithium augmentation treatment with escitalopram, particularly with regard to previously published genetic predictors of lithium augmentation by our group. Of particular interest are the genetic variants of the 5HTTLPR, the GSK3B -50T/C SNP as well as of the intracellular wnt-/beta-catenin pathway. To investigate lithium-dependent gene expression of GSK3B and its correlation to clinical response by comparing mRNA expression before and under lithium treatment. To assess acceptance and life quality of patients treated with escitalopram and lithium.
Secondary endpoints are the GSK3B genotyping and mRNA-expression measurement pre/post lithium-augmentation.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Furthermore we want to explore the influence of childhood trauma (measured by the childhood trauma questionnaire) on genotype dependent differential response to lithium augmentation in depressive patients and we want to explore changes in EEG before and during lithium augmentation in order to find parameters for response prediction (and prediction of genotype dependent differential response).
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E.3 | Principal inclusion criteria |
- unipolar major depressive episode without psychotic symptoms - indication for antidepressant pharmacotherapy - HAMD-17 > 7 for study entry (pre-phase) and step2 (core study) - current treatment with escitalopram monotherapy (at least 10 mg/day) for a minimum of 4 weeks for entry in core study - for entry in core study: insufficient response to escitalopram monotherapy and indication for lithium-augmentation therapy - age 18-70 (male or female) - written informed consent
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E.4 | Principal exclusion criteria |
- psychotic symptoms - pregnant or breastfeeding patients, women of childbearing potential who are not using chemical or mechanical contraception - patients with any contraindication for the treatment with lithium (e.g. severe renal insufficiency) - patients with secondary depression due to another axis-I-comorbidity or non-psychiatric condition - diagnosis of dementia or organic brain disorder - diagnosis of substance dependency with current consumption or consumption in the last 6 months (except caffeine and nicotine) - diagnosis of antisocial personality disorder - participation in other clinical trial (current or in the last 30 days) - persons who are detained legally or officially to an official institution
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | |