Pramipexole and Emotional Processing (PEP)
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|ClinicalTrials.gov Identifier: NCT03681509|
Recruitment Status : Recruiting
First Posted : September 24, 2018
Last Update Posted : April 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Emotions Motivation Reward Dopamine||Drug: Pramipexole Drug: Placebo||Not Applicable|
The dopamine receptor agonist pramipexole has recently been suggested as a potential novel antidepressant drug. While preliminary clinical data hint at its efficacy in treating depressive symptoms, our current understanding of its impact on neurocognitive processes is relatively limited. This is in part because, so far, mechanistic studies have largely focused on the effects of single-dose treatments. However acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically.
Aim of study:
To explore and characterise the effects of a 12 to 15 day regime of pramipexole on behavioural and neural measures of reward learning, emotional information processing, motivational invigoration, and subjective experience.
Using a double-blind, parallel-group design, forty healthy volunteers (male and female, aged 18 to 45 years) will be randomly allocated to a 12 to 15 day regime of either pramipexole (maximum daily dose of 1.0 mg pramipexole salt) or placebo. At baseline and after 12 to 15 days of treatment, a set of previously established cognitive tasks and questionnaires tapping into reward learning, emotional information processing, motivational invigoration and subjective experience will be administered. Furthermore, at 12 to 15 days of treatment, all participants will undergo functional magnetic resonance imaging to compare neural responses to reward- and emotion-related information.
Our working hypothesis is that pramipexole will enhance reward sensitivity, motivational invigoration and hedonic experience and might positively bias emotional information processing.
This will be the first study to broadly explore and characterise the neurocognitive effects of pramipexole administered for a clinically relevant time period. The results of the study will add to our understanding of the cognitive mechanisms through which pramipexole could exert both its beneficial as well as its adverse clinical effects.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||The Effects of the Dopamine Receptor Agonist Pramipexole on Reward and Emotion Related Information Processing in Healthy Volunteers|
|Actual Study Start Date :||September 1, 2018|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||September 2019|
Maximum daily dose: 1.0 mg of pramipexole salt
Placebo Comparator: Placebo
Lactose placebo capsule
- Change in reward sensitivity on a reinforcement learning task between baseline and final day of assessment [ Time Frame: Completed at day 12 to 15 of treatment ]Participants are shown two distinct abstract shapes and have to choose one of them. On each trial, one of the two shapes is associated with a 'win' (resulting in a small monetary gain) and one with a 'loss' (resulting in a small monetary loss). The two outcomes are independent (knowing the location of the win provides no information about the location of the loss). During the task, the information content of the outcomes is manipulated independently by varying the volatility of their occurrence (three conditions: 'win volatile, loss volatile', 'win stable, loss volatile', 'win volatile, loss stable'). Using trial and error, participants have to learn the stimulus-outcome associations and use their knowledge to maximise monetary earnings. Choices are made via button-press. Choice, choice reaction time and pupillary dilation in response to outcome presentation are recorded. By fitting a computational model, reward sensitivity is estimated.
- Change in performance in a facial expression recognition task [ Time Frame: Completed at day 12 to 15 of treatment ]Participants are presented with individual pictures of facial expressions of emotions. Each presented face displays one of six basic emotions (anger, disgust, fear, happiness, sadness, or surprise). Each emotional expression is presented at different levels of intensity which have been created by combining shape and texture features of the two extremes "neutral" (0%) and "full prototypical emotion" (100%) to varying degrees. Examples of neutral facial expressions are presented as well. Participants are instructed to correctly classify each facial expression as angry, disgusted, fearful, happy, sad, surprised or neutral both as quickly and as accurately as possible. Responses are made by pushing one out of seven labelled keys on a response box. Hit rates, false alarm rates, and reaction times for correct classifications are measured separately for each emotion.
- Change in performance in an emotional categorisation task [ Time Frame: Completed at day 12 to 15 of treatment ]Participants are presented with positive and negative personality descriptors and are asked to classify the valence of each word. These words describe either extremely agreeable/positive characteristics (e.g. "cheerful", "honest", "optimistic") or extremely disagreeable/negative characteristics (e.g. "domineering", "untidy", "hostile") and are presented individually in the centre of the screen. Participants are instructed to imagine themselves overhearing someone describing them with each of the words and to indicate as quickly and accurately as possible whether they would like or dislike to be described with each of the words. Responses are made by pressing a correspondingly labelled key on a button box. Reaction times for correct classifications are measured separately for positive and negative words.
- Change in performance in an emotional faces dot probe task [ Time Frame: Completed at day 12 to 15 of treatment ]Pictures of positive and negative emotional stimuli (happy and fearful facial expressions) are presented individually together with a matched neutral stimulus (neutral face). On each trial, one stimulus is shown above and the other below a central fixation point. Subsequently, a probe appears behind one of the stimuli and participants have to correctly classify the probe as quickly and as accurately as possible. Stimuli can be masked (i.e. presented very briefly and followed by a jumbled face) or unmasked (i.e. presented for a longer period without a subsequent masking stimulus). Reaction times for correct responses are recorded and vigilance scores are calculated for masked and unmasked positive and negative stimuli by subtracting reaction time data from trials when the probe appeared in the same position as the emotional stimulus (congruent trials) from trials when the probe appeared in the opposite position to the emotional stimulus (incongruent trials).
- Change in performance in an emotional recall task [ Time Frame: Completed at day 12 to 15 of treatment ]Following a delay period after the emotional categorization task (about 15 min), emotional recall memory is assessed. Participants are asked to recall and write down as many words as possible from the emotional categorization task. Numbers of correctly and incorrectly recalled positive and negative words are measured.
- Amygdala BOLD signal in response to positive and negative emotional faces [ Time Frame: Completed at day 12 to 15 of treatment ]Participants are presented with pictures of positive and negative facial expressions of emotions during functional magnetic resonance imaging. Participants are asked to correctly identify the gender of each face. BOLD signal in the amygdala in response to positive and negative emotional stimuli is measured.
- Change in performance in a probabilistic instrumental learning task [ Time Frame: Completed at day 12 to 15 of treatment ]In each trial, participants are presented with one out of two pairs of symbols. One pair of symbols is a 'win' condition in which one symbol (the 'correct' one) has a 70% chance to win a small monetary reward and a 30% chance to win nothing, while the other symbol (the 'wrong' one) has a 30% chance to win and a 70% chance to win nothing. The other pair of symbols is a 'loss' condition in which one symbol (the 'correct' one) has a 70% chance to lose nothing and a 30% chance to lose a small monetary reward, while the other symbol (the 'wrong' one) has a 70% chance to lose and a 30% chance to lose nothing. Participants are asked to choose one symbol in each pair such that they maximise their payoff. Participants have to learn the stimulus-outcome associations by trial and error such that they consistently choose the symbol with the high-probability win and low-probability loss. Responses are made via button press. Choice, reaction time, and payoff are measured.
- Change in performance in a motivational vigour task [ Time Frame: Completed at day 12 to 15 of treatment ]On each trial, participants are asked to fixate on the center of a computer screen. Following that, they are presented with a cue that provides information about how reward will be determined in that trial. Reward is determined according to one of the following four conditions: (a) 'performance-based reward' (fastest 50% of trials rewarded), (b) 'random reward' (50% small monetary reward and 50% no reward, regardless of performance), (c) 'guaranteed reward' (a fixed small monetary reward, regardless of performance), (d) 'guaranteed absence of reward' (no reward, regardless of performance). Subsequently, a target appears on either the left or the right side of the screen and participants have to move their eyes as quickly as possible towards the target. Participants are then informed about their speed and reward for the task. Saccade velocity and pupillary dilation in response to outcome are recorded.
- Subjective taste experience [ Time Frame: Completed at day 12 to 15 of treatment ]Participants are provided with standardized samples of different taste qualities (sweet, sour, bitter, salty) at four different concentrations. Participants are asked to correctly identify the taste quality of each sample and indicate on a visual analogue perceived pleasantness and disgustingness of each sample.
- Change in subjective experience of pleasure [ Time Frame: Completed at day 12 to 15 of treatment ]Snaith-Hamilton Pleasure Scale, standard questionnaire to assess subjective experience of pleasure
- BOLD signal in the ventral striatum, orbitofrontal cortex and anterior cingulate cortex in response to positive and negative outcomes in a probabilistic instrumental learning task [ Time Frame: Completed at day 12 to 15 of treatment ]Participants perform the same probabilistic instrumental learning task mentioned above while fMRI is conducted. BOLD signal in the ventral striatum and prefrontal cortex in response to positive and negative outcomes is measured.
- Change in subjective mood and energy [ Time Frame: Completed at day 12 to 15 of treatment ]Zersen's Befindlichkeits-Skala
- Change in positive and negative affect [ Time Frame: Completed at day 12 to 15 of treatment ]Positive and Negative Affect Schedule
- Change in subjective anxiety [ Time Frame: Completed at day 12 to 15 of treatment ]State-Trait Anxiety Inventory
- Change in subclinical depressive symptoms [ Time Frame: Completed at day 12 to 15 of treatment ]Beck Depression Inventory
- Change in happiness levels [ Time Frame: Completed at day 12 to 15 of treatment ]Oxford Happiness Questionnaire
- Change in subjective experience of pleasure 2 [ Time Frame: Completed at day 12 to 15 of treatment ]Temporal Experience of Pleasure Scale
- Assessment of drug-induced side effects [ Time Frame: Completed at day 12 to 15 of treatment ]Side effect questionnaire
- Change in impulsive compulsive symptoms [ Time Frame: Completed at day 12 to 15 of treatment ]Adapted Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease Rating Scale
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03681509
|Contact: Alexander Kaltenboeck, Dr.med.univ.||+44 1865 firstname.lastname@example.org|
|Contact: Michael Browning, MB.BS||+44 1865 email@example.com|
|Dept of Psychiatry, University of Oxford||Recruiting|
|Oxford, Oxfordshire, United Kingdom, OX3 7JX|
|Contact: Michael Browning, MB.BS +44 (0)1865 6183161 firstname.lastname@example.org|
|Principal Investigator: Michael Browning, MB.BS|
|Principal Investigator:||Michael Browning, MB.BS||University of Oxford|