Clinical trial NCT03681509: Pramipexole and Emotional Processing
Official title: The Effects of the Dopamine Receptor Agonist Pramipexole on Reward and Emotion Related Information Processing in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Emotions
Motivation
Reward
Dopamine
Keywords: Pramipexole
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2018-09-24
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Change in reward sensitivity on a reinforcement learning task between baseline and final day of assessment
timeFrame: Completed at day 12 to 15 of treatment
Secondary outcomes:
measure: Change in performance in a facial expression recognition task
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in performance in an emotional categorisation task
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in performance in an emotional faces dot probe task
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in performance in an emotional recall task
timeFrame: Completed at day 12 to 15 of treatment
measure: Amygdala BOLD signal in response to positive and negative emotional faces
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in performance in a probabilistic instrumental learning task
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in performance in a motivational vigour task
timeFrame: Completed at day 12 to 15 of treatment
measure: Subjective taste experience
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in subjective experience of pleasure
timeFrame: Completed at day 12 to 15 of treatment
measure: 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
timeFrame: Completed at day 12 to 15 of treatment
Other outcomes:
measure: Change in subjective mood and energy
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in positive and negative affect
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in subjective anxiety
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in subclinical depressive symptoms
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in happiness levels
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in subjective experience of pleasure 2
timeFrame: Completed at day 12 to 15 of treatment
measure: Assessment of drug-induced side effects
timeFrame: Completed at day 12 to 15 of treatment
measure: Change in impulsive compulsive symptoms
timeFrame: Completed at day 12 to 15 of treatment
Locations:
city: Oxford
country: United Kingdom
facility: Dept of Psychiatry, University of Oxford
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Michael Browning, MB.BS
role: PRINCIPAL_INVESTIGATOR
References: