Pramipexole and Emotional Processing

NCT03681509 | Completed

• 1 other identifier: MS IDREC R07790
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Emotions; Motivation; Reward; Dopamine

Keywords

Pramipexole

Outcome Measures

Primary Outcomes (1)

• 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.

  Completed at day 12 to 15 of treatment

Secondary Outcomes (10)

• Change in performance in a facial expression recognition task

  Completed at day 12 to 15 of treatment

• Change in performance in an emotional categorisation task

  Completed at day 12 to 15 of treatment

• Change in performance in an emotional faces dot probe task

  Completed at day 12 to 15 of treatment

• Change in performance in an emotional recall task

  Completed at day 12 to 15 of treatment

• Amygdala BOLD signal in response to positive and negative emotional faces

  Completed at day 12 to 15 of treatment

Other Outcomes (8)

• Change in subjective mood and energy

  Completed at day 12 to 15 of treatment

• Change in positive and negative affect

  Completed at day 12 to 15 of treatment

• Change in subjective anxiety

  Completed at day 12 to 15 of treatment

Study Arms (2)

Pramipexole

EXPERIMENTAL

Maximum daily dose: 1.0 mg of pramipexole salt

Drug: Pramipexole

Placebo

PLACEBO COMPARATOR

Lactose

Drug: Placebo

Interventions

Pramipexole DRUG

Pramipexole

Pramipexole

Placebo DRUG

Lactose placebo capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Dept of Psychiatry, University of Oxford

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

MeSH Terms

Interventions

Pramipexole

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael Browning, MB.BS

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 24, 2018
• Study Start: September 1, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: March 24, 2020

Record last verified: 2020-03

Locations

GB (1)