EmotionsPEPNCT03681509
Pramipexole and Emotional Processing
A study testing Pramipexole in people with Emotions and Motivation, run by University of Oxford at 1 site in United Kingdom.
Trial summary
The dopamine 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Emotions, Motivation, Reward
- What is being tested?
- Pramipexole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2018to 1 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female
- Age: 18 to 45 years
- Good physical and mental health
- Participant is willing and able to give informed consent for participation in the study
- Sufficient knowledge of English language to understand and complete study tasks
- Willingness to refrain from driving, cycling, or operating heavy machinery if necessary while taking part in the study
- Willingness to refrain from drinking while taking part in the study.
Who cannot join
- Current or past psychiatric disorder (e.g. depression, bipolar disorder etc.)
- First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
- BMI not between 18 and 30
- History of unexplained hallucinations or impulse control problems (e.g. pathological gambling)
- Any severe medical condition not stabilized at the time of the experiment (e.g. cardiovascular disease, epilepsy, asthma etc.)
- Severe heart or blood vessel disease
Show all 22Show fewer
- Postural hypotension
- Any history of seizures
- Lactose intolerance
- Any current or past physical illness that has the potential to significantly affect mental functioning (e.g. epilepsy, hypothyroidism, Parkinson's disease, multiple sclerosis etc.)
- Pregnant, or lactating woman
- Sexually active woman who does not use any medically accepted method of contraception
- Current or previous intake (last three months) of any medication that has a significant potential to affect mental functioning (e.g. benzodiazepines, antidepressants, neuroleptics etc.)
- Any intake of recreational drugs in the last 3 months (e.g. marijuana, ecstasy etc.)
- Regular alcohol consumption of more than 14 units a week or excessive alcohol consumption up to three days before the experiment
- Regular smoker (> 5 cigarettes per day)
- Excessive caffeine user (> 6 caffeinated drinks per day)
- History of recurrent rashes or history of allergic reactions to relevant substances (pramipexole treatment, placebo treatment, taste samples)
- Previous participation in a study using the same or similar tasks
- Any contraindication to magnetic resonance imaging (e.g. metallic implant, severe claustrophobia)
- Current participation in another study
- In the researcher's opinion participation in the study could be harmful or severely distressing to the participant (e.g. intolerance of side effects) or the participant is not able to follow instructions or complete study tasks
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Dept of Psychiatry, University of Oxford
Oxford, Oxfordshire, OX3 7JX
About this study
Official title: The Effects of the Dopamine Receptor Agonist Pramipexole on Reward and Emotion Related Information Processing in Healthy Volunteers
The dopamine 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 mechanistic studies have largely focused on the effects of single-dose treatments. However, such acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically. This study therefore aims to explore and characterise the neurocognitive effects of more prolonged pramipexole treatment. Forty healthy volunteers will be randomly allocated to 12 to 15 days of treatment with either pramipexole or placebo. Study participants as well as researchers will be blinded as to which treatment is used. Before and after treatment all participants will perform a set of psychological tasks and questionnaires evaluating reward-based learning, emotional information processing, motivational vigour and subjective experience. Furthermore, functional magnetic resonance imaging (fMRI) will be used to compare neural activity during emotion and reward processing between the two treatment groups. We hypothesises that pramipexole might enhance reward sensitivity, motivational vigour, and pleasure experience and could induce positive biases in emotional information processing.
Read the detailed description
Background:
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.
Methods:
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.
Hypotheses:
Our working hypothesis is that pramipexole will enhance reward sensitivity, motivational invigoration and hedonic experience and might positively bias emotional information processing.
Implications:
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.
- Conditions
- Emotions, Motivation, Reward, Dopamine
- Being tested
- Pramipexole, Placebo
- Keywords
- Pramipexole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PramipexoleDrug
Pramipexole
PlaceboDrug
Lactose placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Pramipexole | Experimental | Maximum daily dose: 1.0 mg of pramipexole salt Receives: Drug: Pramipexole |
| Placebo | Placebo comparator | Lactose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in reward sensitivity on a reinforcement learning task between baseline and final day of assessment
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.
Measured: Completed at day 12 to 15 of treatment
Secondary outcomes (10)
Change in performance in a facial expression recognition task
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.
Measured: Completed at day 12 to 15 of treatment
Change in performance in an emotional categorisation task
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.
Measured: Completed at day 12 to 15 of treatment
Change in performance in an emotional faces dot probe task
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).
Measured: Completed at day 12 to 15 of treatment
Change in performance in an emotional recall task
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.
Measured: Completed at day 12 to 15 of treatment
Amygdala BOLD signal in response to positive and negative emotional faces
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.
Measured: Completed at day 12 to 15 of treatment
Change in performance in a probabilistic instrumental learning task
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.
Measured: Completed at day 12 to 15 of treatment
Change in performance in a motivational vigour task
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.
Measured: Completed at day 12 to 15 of treatment
Subjective taste experience
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.
Measured: Completed at day 12 to 15 of treatment
Change in subjective experience of pleasure
Snaith-Hamilton Pleasure Scale, standard questionnaire to assess subjective experience of pleasure
Measured: Completed at day 12 to 15 of treatment
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
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.
Measured: Completed at day 12 to 15 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start1 Sep 2018
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EmotionsStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Browning, MB.BS, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03681509
- Sponsor's protocol ID
- MS IDREC R07790
- Acronym
- PEP
- Status last verified
- Mar 2020
- First submitted
- 19 Sep 2018
- Last updated
- 24 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of the Dopamine Receptor Agonist Pramipexole on Reward and Emotion Related Information Processing in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03681509
- Acronym / sponsor ID
- PEP / MS IDREC R07790
- Conditions
- Emotions, Motivation, Reward, Dopamine
- Keywords
- Pramipexole
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 24 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The dopamine 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 mechanistic studies have largely focused on the effects of single-dose treatments. However, such acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically. This study therefore aims to explore and characterise the neurocognitive effects of more prolonged pramipexole treatment. Forty healthy volunteers will be randomly allocated to 12 to 15 days of treatment with either pramipexole or placebo. Study participants as well as researchers will be blinded as to which treatment is used. Before and after treatment all participants will perform a set of psychological tasks and questionnaires evaluating reward-based learning, emotional information processing, motivational vigour and subjective experience. Furthermore, functional magnetic resonance imaging (fMRI) will be used to compare neural activity during emotion and reward processing between the two treatment groups. We hypothesises that pramipexole might enhance reward sensitivity, motivational vigour, and pleasure experience and could induce positive biases in emotional information processing.
Detailed description
Background:
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.
Methods:
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.
Hypotheses:
Our working hypothesis is that pramipexole will enhance reward sensitivity, motivational invigoration and hedonic experience and might positively bias emotional information processing.
Implications:
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pramipexole | Experimental | Drug: PramipexoleMaximum daily dose: 1.0 mg of pramipexole salt |
| Placebo | Placebo comparator | Drug: PlaceboLactose |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or female
- Age: 18 to 45 years
- Good physical and mental health
- Participant is willing and able to give informed consent for participation in the study
- Sufficient knowledge of English language to understand and complete study tasks
Key exclusion criteria (22 listed)
- Current or past psychiatric disorder (e.g. depression, bipolar disorder etc.)
- First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
- BMI not between 18 and 30
- History of unexplained hallucinations or impulse control problems (e.g. pathological gambling)
- Any severe medical condition not stabilized at the time of the experiment (e.g. cardiovascular disease, epilepsy, asthma etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PramipexolePramipexole | Drug | Pramipexole |
| PlaceboLactose placebo capsule | Drug | Placebo |
Primary outcome
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.
10 secondary outcomes
Change in performance in a facial expression recognition task
Time frame: Completed at day 12 to 15 of treatment
Change in performance in an emotional categorisation task
Time frame: Completed at day 12 to 15 of treatment
Change in performance in an emotional faces dot probe task
Time frame: Completed at day 12 to 15 of treatment
Change in performance in an emotional recall task
Time frame: Completed at day 12 to 15 of treatment
Amygdala BOLD signal in response to positive and negative emotional faces
Time frame: Completed at day 12 to 15 of treatment
Change in performance in a probabilistic instrumental learning task
Time frame: Completed at day 12 to 15 of treatment
Change in performance in a motivational vigour task
Time frame: Completed at day 12 to 15 of treatment
Subjective taste experience
Time frame: Completed at day 12 to 15 of treatment
Change in subjective experience of pleasure
Time frame: Completed at day 12 to 15 of treatment
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Browning, MB.BS principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pramipexole in people with Emotions and Motivation, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2020.