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 |
The main objective of 4-week, double-blind and subsequent 8-week, open-label studies is to compare efficacy and tolerability of transcranial direct
current stimulation and venlafaxine in the acute treatment of depression and relapse prevention. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study is to evaluate efficacy of the change of the prefrontal theta cordance in the prediction of response to venlafaxine and transcranial direct current stimulation and to map basal status and changes associated with treatment with both interventions in terms of various EEG parameters and functional connectivity (LORETA, fMRI) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients suffering from Major depressive disorder (recurrent or single episode) diagnosed
according to Diagnostic and Statistical Manual of the American Psychiatric Association-IV. revision
criteria, confirmed using The Mini-International Neuropsychiatric Interview - M.I.N.I., Czech version
5.0.0.
2. Patients fulfilling at least Stage I (≥1 previous, unsuccessful, adequate, antidepressant treatment)
criteria for resistant depression according to Thase and Rush
3. The mental ability to understand and sign Informed Consent Form.
4. The score in the Montgomery and Åsberg Rating Scale (MADRS) ≥25 and the score in Clinical
Global Impression ≥4.
5. Inpatients in the double-blind phase of treatment.
6. Age between 18 and 65 years.
7. Right handedness. |
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E.4 | Principal exclusion criteria |
1. Psychiatric comorbidity on axis I and II according to DSM IV in the 6 months before enrollment to
the study.
2. Psychotic, bipolar disorder or dementia in the history
3. Contraindications of venlafaxine treatment according to SPC.
4. Contraindications of MRI (metallic plates in the head, applied pacemaker or other electronic
stimulation devices, etc.).
5. Contraindications of tDCS (skin disease, superficial injuryand fracture or infraction of skull in the
stimulation area, epilepsy, metallic plates in the head)
6. Pregnancy or breast-feeding.
7. Patients with severe somatic disorders (cardiovascular disease, neoplasms, endocrinology
disorders etc.) that could be associated with depression due to somatic diseases.
8. Patients treated with electroconvulsive therapy less than 3 month before enrollment or suffering
from neurologic disorder (e.g., epilepsy, head trauma with loss of consciousness) and patients using
any treatment which can strongly affect EEG.
9. Application of other concomitant medication that is not allowed in protocol (e.g. antipsychotics,
mood stabilizers etc.).
10. Unsuccessful treatment with venlafaxine or tDCS in the current episode of MDD.
11. Fluoxetine treatment before the enrollment to the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Response to treatment will be defined as reduction of total MADRS score ≥ 50% after 4 weeks of treatment in the acute phase of the study.
2.elapse will be defined as the score≥20 points in the MADRS in combination with score 4 or more points in the CGI at the time of follow-up visits or
change of antidepressant treatment due to substantial worsening of clinical status in the follow-up phase of the study (8 weeks) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.Response: at the end of the acute phase of the study (4 weeks)
2.Relapse: at the end of the follow- up phase of the study (8 weeks) or at the time of subject´s drop-out |
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E.5.2 | Secondary end point(s) |
1. Decrease of prefrontal theta cordance value at week 1 comparing to baseline in subsequent responders and non-responders in the acute phase of the study
2. The change of EEG parameters and functional connectivity (LORETA, fMRI) in responders and non-responders in the acute phase of the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Decrease of prefrontal theta cordance value at week 1 comparing to baseline in subsequent responders and non-responders - week 1
2. The change of EEG parameters and functional connectivity (LORETA, fMRI) in responders and non-responders - week 1, week 4 of the acute phase of the study. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
transcranial direct stimulation |
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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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |