Clinical trial NCT04130087: Selegiline and Reward Processing
Official title: The Effects of a Single Dose on Reward and Emotional Processing in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Healthy
Keywords: Reward
Selegiline
Cognition
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2019-10-17
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo controlled trial.

27 participants will be allocated to receive a single 10mg of selegiline and the same number will receive a single dose of placebo (lactose tablet.)
Primary purpose: BASIC_SCIENCE

Brief summary: There has been growing interest in the relationship between reward processing and clinical symptoms of depression such as anhedonia (loss of interest and response to pleasurable activities).

The aim of the study is to investigate the acute effects of a single dose of selegiline (an irreversible monoamine oxidase B inhibitor) on reward and emotional processing in healthy volunteers.

Detailed description: There has been growing interest in the relationship between reward processing and clinical symptoms of depression such as anhedonia (loss of interest and response to pleasurable activities). Studies in animals have suggested that the neurotransmitter, dopamine, plays a key role in reward processing. This has given rise to the suggestion that in depression, decrements in dopamine activity lead to impaired reward processing which cause symptoms such as anhedonia and low motivation.

Research in humans into dopamine and reward is limited by suitable pharmacological means to manipulate dopamine activity safely and effectively.

To our knowledge, no previous research has studied the effects of acute administration of the licensed drug, selegiline, on reward and emotional processing. However, a single dose of selegiline effectively inhibits monoamine oxidase B (MAO-B), which should lead to increased dopamine availability in the CNS. Therefore, selegiline may be a useful tool to explore the effect of modifying dopamine availability on reward processing. Acquiring such knowledge through this study could assist in the clinical use of MAO-B inhibition as a target to ameliorate symptoms such as anhedonia as well as increasing our general understanding of reward processing in healthy individuals.

The aim of this study is to explore the effects of acute administration of a standard (10mg) dose of selegiline on reward and emotional processing versus a placebo, in healthy volunteers. At this dose selegiline only has an -MAO-B function therefore the specific impact of MAO-B blockade on reward and emotional processing can be explored.

Research Question: What effect will the administration of a single dose of selegiline have on reward and emotional processing in healthy volunteers?

Eligibility criteria: Inclusion Criteria:

* 18-40 years of age
* Able to give informed consent for study participation
* Sufficient fluency in English to understand and complete the neuropsychological tasks

Exclusion Criteria:

* Current usage of other regular medication (including the contraceptive pill, the Depo-Provera injection or the progesterone implant, and hormone replacement therapy)
* Any past or current Axis 1 DSM-IV psychiatric disorder
* Significant medical condition
* Pulse \< 60 beats per minute at baseline screening
* Current or past gastro-intestinal disorder or irritable bowel syndrome
* Current pregnancy or breastfeeding
* Known lactate deficiency or any other problem absorbing lactose, galactose or glucose
* Current or past history of drug or alcohol dependency
* Participation in a psychological or medical study involving the use of medication within the last 3 months
* Previous participation in a study using the same, or similar, emotional processing tasks
* Smoker \> 5 cigarettes per day
* Typically drinks \> 6 caffeinated drinks per day

Primary outcomes:
measure: Total monetary amount won in reward learning task.
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Reaction times (milliseconds) in reward learning task
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Reward sensitivity in reward learning task
timeFrame: Tested one hour after selegiline/placebo ingestion
Secondary outcomes:
measure: Reaction Time (milliseconds) on the Faces Dot Probe Task (FDOT)
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Reaction time (milliseconds) in an Emotional Categorisation Task (ECAT)
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Performance (number of words recalled) in an emotional recall task (EREC)
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Percentage Accuracy(%) on facial expression recognition task (FERT)
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Reaction times (milliseconds) on facial expression recognition task (FERT)
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Percentage accuracy (%) in an Emotional Recognition Memory Task (EMEM)
timeFrame: Tested one hour after selegiline/placebo ingestion
measure: Reaction times (milliseconds) in Emotional Recognition Memory Task (EMEM)
timeFrame: Tested one hour after selegiline/placebo ingestion
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: University of Oxford
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Catherine Harmer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S. Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry. 2013 Apr 1;73(7):639-45. doi: 10.1016/j.biopsych.2012.10.014. Epub 2012 Dec 8.
citation: Admon R, Pizzagalli DA. Dysfunctional Reward Processing in Depression. Curr Opin Psychol. 2015 Aug 1;4:114-118. doi: 10.1016/j.copsyc.2014.12.011.
citation: Krystal JH, Sanacora G, Duman RS. Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry. 2013 Jun 15;73(12):1133-41. doi: 10.1016/j.biopsych.2013.03.026.
citation: Machado-Vieira R, Salvadore G, Diazgranados N, Zarate CA Jr. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther. 2009 Aug;123(2):143-50. doi: 10.1016/j.pharmthera.2009.02.010. Epub 2009 May 3.
citation: Heinonen EH, Anttila MI, Nyman LM, Pyykko KA, Vuorinen JA, Lammintausta RA. Inhibition of platelet monoamine oxidase type B by selegiline. J Clin Pharmacol. 1997 Jul;37(7):597-601. doi: 10.1002/j.1552-4604.1997.tb04341.x.