E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
There are no medical conditions or diseases under investigation. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Not possible to specify |
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 |
We aim to investigate whether the dopamine receptor D4 (DRD4) genotype confers differential susceptibility to the effects of early life stress, on caregiving behavior in adults. We also aim to study whether DRD4 genotype and resting frontal asymmetry confer differential susceptibility to effects of a dopaminergic pharmacological intervention on caregiving-related neurocognitive processes, behaviors, and attitudes. The following questions will be addressed: 1. What is the relationship between DRD4 genotype and adult empathy and prosocial behavior, and does early life experience moderate this effect? 2. What is the effect of L-Dopa administration (a pharmacological intervention that heightens levels of dopamine) on parenting-related neurocognitive processes, behaviors, and attitudes? 3. Does the DRD4 genotype moderate the efficacy of the pharmacological intervention? 4. Can resting frontal asymmetry serve as an endophenotype for differential susceptibility?
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E.2.2 | Secondary objectives of the trial |
Rigorous statistical probing will be conducted, including the use of simulations to test the integrity of the data. Results of these statistical assessments will be used to correct the data accordingly. These analyses will help to improve the quality of data-analysis and conclusions, and provide statistical guidelines for future data-analysis of similar designs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
healthy, female, 18 years old or older, of caucasian descent |
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E.4 | Principal exclusion criteria |
pregnancy, breastfeeding, drug or alcohol abuse, prior psychiatric or neurological disorder,use of medication (except oral contraceptives), existing medical condition |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Theory of Mind. An adult version of the Reading the Mind in the Eyes Test will be carried out, to determine the baseline level of interpretation of emotion. -Prosociality. - Resting frontal asymmetry. Participants’ resting EEG will be recorded and an asymmetry index will be computed (see below). As described above, we will investigate whether resting frontal alpha asymmetry can be considered an endophenotype for differential susceptibility. - Neural indices of the processing of and attention to infant faces and sounds. ERP components indicative of processing depth and attention will be computed from the EEG recorded while participants listen to infant sounds and view infant faces (see below). EEG asymmetry in response to faces and sounds, as a measure of approach-withdrawal responses to these stimuli, will also be computed (see below). We will study effects of L-Dopa on these neural indices, and investigate whether L-Dopa effects are moderated by the DRD4 genotype and resting frontal asymmetry. In addition, we will investigate whether changes in neural indices after L-Dopa administration mediate changes in behavioral measures (sensitivity, interpretation of infant cues, caregiving attitudes, empathy). - Cardiac indices of arousal in response to infant faces and sounds. Cardiac indices indicating sympathetic and parasympathetic activity will be computed from the ECG and ICG recorded while participants listen to infant sounds and view infant faces (see below). We will study effects of L-Dopa on these neural indices, and investigate whether L-Dopa effects are moderated by the DRD4 genotype and resting frontal asymmetry. In addition, we will investigate whether changes in cardiac indices after L-Dopa administration mediate changes in behavioral measures (sensitivity, interpretation of infant cues, caregiving attitudes, empathy). -Mirror-neuron activity. Mirror-neuron activity will be studied using measures derived from the EEG (see below). We will investigate whether potential effects of L-Dopa on these measures are moderated by the DRD4 genotype and resting frontal asymmetry. In addition, we will investigate whether changes in mirror-neuron activity after L-Dopa administration mediate changes in behavioral measures (sensitivity, interpretation of infant cues, caregiving attitudes, empathy). - Sensitivity of caregiving behaviour. The Leiden Infant Simulator Assessment will be used to measure participants’ sensitivity (see below). We will investigate investigate whether potential effects of L-Dopa on sensitivity are moderated by the DRD4 genotype and resting frontal asymmetry. - Interpretation of infant cues. An infant-face version of the Reading the Mind in the Eyes Test will be used to measure participants’ interpretation of infant cues (see below). We will study effects of L-Dopa on this measure, and investigate whether L-Dopa effects are moderated by the DRD4 genotype and resting frontal asymmetry. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Participants will come to the laboratory for two identical experimental sessions, separated by 4 weeks. |
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E.5.2 | Secondary end point(s) |
- Self-reported caregiving attitudes and empathy. We will investigate whether L-Dopa administration affects questionnaire measures (see below) of empathy and caregiving attitudes, and whether potential effects are moderated by genotype and resting frontal asymmetry. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary parameters will be assessed during the same two identical experimental sessions, separated by 4 weeks. |
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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 |
We aim to investigate whether the dopamine receptor D4 (DRD4) genotype confers differential susceptibility to the effects of early life stress, on caregiving behavior in adults. We also aim to study whether DRD4 genotype and resting frontal asymmetry confer differential susceptibility to effects of a dopaminergic pharmacological intervention on caregiving-related neurocognitive processes, behaviors, and attitudes. |
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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 | No |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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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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 |