E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Premenstrual Dysphoric Disorder |
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E.1.1.1 | Medical condition in easily understood language |
Mood disorder with onset of mood and physical symptoms in the luteal phase of the menstrual cycle, a decline in symptom severity after onset of menstruation. |
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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 investigate the neuropsychological underpinnings of PMDD symptoms relief at the brain structural and functional level comparing PMDD patients before and after treatment with escitalopram and considering placebo effects |
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E.2.2 | Secondary objectives of the trial |
to assess the relationship between neural correlates and psychiatric, psychological, endocrine and genetic measures |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
– informed consent – essentially healthy – 18-49 years of age – have a regular menstrual cycle (25-31 days) in the opinion of the investigator – accept to undergo brain magnetic resonance imaging assessment – confirmed PMDD according to DSM-IV verified in two menstrual cycles for the patient group
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E.4 | Principal exclusion criteria |
- hormonal contraceptive use within three months prior to inclusion - pregnancy, breast feeding - presence of other ongoing psychiatric disorders - treatment with benzodiazepines, or other psychotropic drugs (including SSRI) within six months prior to inclusion - previous history of non-response to SSRI treatment - presence of other major diseases - visual impairment (> 5 degrees myopic/hyperopic or profound astigmatism), previous brain surgery, profound fear of confined spaces, and regular contraindications for magnetic resonance imaging |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints • Brain emotional stimuli processing assessed using functional magnetic resonance imaging (fMRI) by the following tasks: emotion discrimination task (Hariri task, EDT), point subtraction aggression paradigm (PSAP), and reward task (IOWA). • Brain resting state activity (rsMRI); • Brain morphology measured by MRI.
Variables used to asses treatment response • Treatment effectiveness (difference in mean DRSP scores for core PMDD symptoms during the last two weeks of each treatment cycle, and change from baseline in mean DRSP scores, as well as response and remission according to DSM criteria).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
pretreatment and during the second and last treatment cycle |
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E.5.2 | Secondary end point(s) |
• Treatment related changes in quality of life (EDQ5). • The Montgomery-Asberg Depression Rating Scale (MADRS), the State Anxiety Inventory (STAI), the Swedish universities Scale of Personality (SSP), the Aggression Questionnaire-revised Swedish version (AQ-RSV), the Positive and negative affect schedule (PANAS); • Transcript and DNA methylation profiles in blood of type-A γ-aminobutyric acid receptor (GABRA), serotonin transporter (5HTT), tryptophan hydroxylase (TPH), monoamine oxidase (MAOA), catechol-o-metyltransferase (COMT), and brain-derived neurotrophic factor (BDNF) genes, and BDNF protein levels: • Blood levels of pregnenolone, 17-OH-pregnenolone, 17-OH-progestyerone, cortisol, cortisone, 11-deoxycortisol, DHEA, allopregnanolone, androstenedione, testosterone, dihydrotestosterone, estrone, estriol, estradiol and (S)-citalopram; bioavailable fraction of hormones in saliva. • Genotype of 5-HTTLPR, TPH2 rs4131347, MAOA-uVNTR, COMT Val158Met, BDNF Val66Met polymorphisms, and tag-SNPs in the GABRA gene;
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
pretreatment and during the second and last treatment cycle |
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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 | 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 |
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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) | 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 | 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 | Yes |
E.8.2.3 | Other | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |