Selegiline and Reward Processing

Healthy Clinical Trial

Official title:

The Effects of a Single Dose on Reward and Emotional Processing in Healthy Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04130087
• Other study ID #: R64689/RE001
• Status: Recruiting
• Phase: N/A
• Start date: September 18, 2019
• Est. completion date: September 10, 2020

Study information

• Verified date: September 2019
• Source: University of Oxford
• Contact: Mayowa Oyesanya, MD
• Phone: 01865 613 176
• Email: mayowa.oyesanya[@]conted.ox.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: September 10, 2020
• Est. primary completion date: September 10, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Selegiline Hydrochloride 10 MG
Single 10mg tablet of Selegiline Hydrochloride
• Placebo
Single Placebo Tablet, identical appearance to experimental tablet.

Locations

Country	Name	City	State
United Kingdom	University of Oxford	Oxford	Oxfordshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

Admon R, Pizzagalli DA. Dysfunctional Reward Processing in Depression. Curr Opin Psychol. 2015 Aug 1;4:114-118. — View Citation

Heinonen EH, Anttila MI, Nyman LM, Pyykkö KA, Vuorinen JA, Lammintausta RA. Inhibition of platelet monoamine oxidase type B by selegiline. J Clin Pharmacol. 1997 Jul;37(7):597-601. — View 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. Review. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total monetary amount won in reward learning task.	During this task participants have to repeatedly choose between 2 options. On each trial one of the options, if chosen by the participant, will result in the participant winning money. The participant simply has to learn which is the best option to choose so as to win as much money as possible.	Tested one hour after selegiline/placebo ingestion
Primary	Reaction times (milliseconds) in reward learning task	During this task participants have to repeatedly choose between 2 options. On each trial one of the options, if chosen by the participant, will result in the participant winning money. The participant simply has to learn which is the best option to choose so as to win as much money as possible.	Tested one hour after selegiline/placebo ingestion
Primary	Reward sensitivity in reward learning task	During this task participants have to repeatedly choose between 2 options. On each trial one of the options, if chosen by the participant, will result in the participant winning money. The participant simply has to learn which is the best option to choose so as to win as much money as possible.	Tested one hour after selegiline/placebo ingestion
Secondary	Reaction Time (milliseconds) on the Faces Dot Probe Task (FDOT)	The FDOT assesses attention to positive versus negative stimuli using a reaction time measure. Two faces are presented vertically on the computer screen and replaced by a pair of dots, to which the participant has to respond by indicating whether the dots are vertically or horizontally aligned. On some trials, one of the two faces presented has an emotional expression (fearful or happy). On half of the trials, the faces are presented very briefly and immediately replaced by a jumbled face mask. The reaction time to respond to the dots can be used as a measure of attention to the emotional faces.	Tested one hour after selegiline/placebo ingestion
Secondary	Reaction time (milliseconds) in an Emotional Categorisation Task (ECAT)	The ECAT assesses speed to respond to positive and negative self-referent personality descriptors. Sixty personality characteristics (30 per valence) selected to be disagreeable (eg, sneering, untidy, hostile) or agreeable (eg, cheerful, honest, optimistic) are presented. The participants are asked whether they would like or dislike to be referred to as each characteristic.	Tested one hour after selegiline/placebo ingestion
Secondary	Performance (number of words recalled) in an emotional recall task (EREC)	The EREC is a surprise free recall task to assess the incidental encoding of emotional stimuli. Participants are asked to recall as many of the words previously presented in the ECAT task (See Outcome Measure 4) as they can. The relative recall of positive versus negative words gives a measure of emotional biases in memory. This task is not computerised - participants write the recalled words on paper.	Tested one hour after selegiline/placebo ingestion
Secondary	Percentage Accuracy(%) on facial expression recognition task (FERT)	The FERT assesses the interpretation of facial expressions. Faces with seven different basic emotions (happiness, fear, anger, disgust, sadness, surprise, neutral) are displayed on the screen and participants are required to indicate the expression on the face via a button-press. Different intensity levels of each emotion are presented, which increases the ambiguity of the facial expression and the sensitivity of the task.	Tested one hour after selegiline/placebo ingestion
Secondary	Reaction times (milliseconds) on facial expression recognition task (FERT)	The FERT assesses the interpretation of facial expressions. Faces with seven different basic emotions (happiness, fear, anger, disgust, sadness, surprise, neutral) are displayed on the screen and participants are required to indicate the expression on the face via a button-press. Different intensity levels of each emotion are presented, which increases the ambiguity of the facial expression and the sensitivity of the task.	Tested one hour after selegiline/placebo ingestion
Secondary	Percentage accuracy (%) in an Emotional Recognition Memory Task (EMEM)	The EMEM measures recognition memory for affective words. Participants are presented with a series of words comprising the pleasant and unpleasant personality words that were previously presented to them in the ECAT, and a set of previously unseen distracter words. For each word, participants are required to report whether they have previously seen the word.	Tested one hour after selegiline/placebo ingestion
Secondary	Reaction times (milliseconds) in Emotional Recognition Memory Task (EMEM)	The EMEM measures recognition memory for affective words. Participants are presented with a series of words comprising the pleasant and unpleasant personality words that were previously presented to them in the ECAT, and a set of previously unseen distracter words. For each word, participants are required to report whether they have previously seen the word.	Tested one hour after selegiline/placebo ingestion