Pharmacological Modulation of Belief Salience

NCT03754062 | Completed Phase 1

• 1 other identifier: HR-16/17-0603
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To provide an initial test of the hypothesis that dopamine mediates the motivational salience of stimuli beyond simple stimulus-reinforcement associations, the researchers propose to undertake a study of the modulation of a) levels of agreement or disagreement with; b) the perceived self- relevance; and c) the perceived interest of propositions expressing beliefs and values in healthy male volunteers using Ii) a dopamine antagonist (the D2-blocker haloperidol), and (ii) a dopamine precursor L-Dopa to increase CNS dopamine transmission. The researchers will also administer the Salience Attribution Task (SAT) which will allow researchers to assess reward-learning processing of simple stimuli using a reaction-time game. This task was utilised by Roiser et al in order to explore whether delusions in medicated patients with schizophrenia were related to impairments in associative learning. The authors hypothesised that associative learning was influenced by D2 receptor blockade. The researchers extend this approach to examine the effect of dopamine modulation on the SAT as a measure of associative learning, a basic neuropsychological process that may be involved in the attribution of salience to beliefs. Finally, the researchers will ask participants to perform a within-subjects dictator game to understand the influence of dopaminergic manipulation of the live attribution of harm intention to partners. The task has been previously validated online. Participants will play against 3 partners in a random order in each drug condition. Each partner will play the participant for 6 trials. One partner will always be fair, one will always be unfair, and one will be 50% unfair. We aim to understand whether potentiating dopamine has an additive effect on the harm intention attributions toward partners, regardless of the behaviour of the partner.

Conditions

Haloperidol; Placebo; L-DOPA

Outcome Measures

Primary Outcomes (3)

• Beliefs and Values Inventory (BVI)

  Change in score between conditions on the BVI. Scores will be summed by item totals within theme (paranormal, religion, morality, politics, and science) and dimension (agreement, self-relevance, and interest).

  12 Months

• Salience Attribution Test (SAT)

  Change in attribution of explicit and implicit salience between conditions on the SAT.

  12 Months

• Within-subjects dictator game

  Participants will play against three different partners, each for six trials. In each trial, the player's partner will have the option to either split or take 10p from the player, so that the player either ends up with 5p or 0p. Players will play against one partner that will always split the money, one that will always take all of the money, and one that will 50% of the time split the money. After each trial, the player will be asked on a scale of 1-100 (1 being not at all and 100 being completely): 1. How much do you think your partner was driven by a desire to increase their own bonus, and 2. How much do you think your partner was driven by a desire to reduce your bonus. Total of a. and b. will be added up for each style of partner for each arm.

  12 Months

Secondary Outcomes (2)

• Big-5 Personality Questionnaire

  6 Months

• Brief Oxford-Liverpool Inventory of Experiences and Feelings

  6 Months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo control

Drug: Placebo - Cap

Haloperidol 3mg

EXPERIMENTAL

Haloperidol

Drug: Haloperidol

L-Dopa 150 mg & Domperidone 10mg

EXPERIMENTAL

L-Dopa

Drug: L-dopa

Interventions

Placebo - Cap DRUG

Administration of Placebo by pill.

Placebo

L-dopa DRUG

Administration of L-dopa by pill.

L-Dopa 150 mg & Domperidone 10mg

Haloperidol DRUG

Administration of Haloperidol by pill.

Haloperidol 3mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males between the ages of 18-65

You may not qualify if:

• History or current psychiatric or neurological illness, history or current serious medical diagnosis, BMI outside of normal/healthy range, smoker over 5 cigarettes per day, recent use of drugs, non-english speaker.

Sponsors & Collaborators

• King's College London: lead
• Medical Research Council: collaborator

Study Sites (1)

Centre for Neuroimaging Sciences

London, W1T 7NF, United Kingdom

Location

Related Publications (3)

• Schmidt K, Roiser JP. Assessing the construct validity of aberrant salience. Front Behav Neurosci. 2009 Dec 23;3:58. doi: 10.3389/neuro.08.058.2009. eCollection 2009.

  PMID: 20057930 RESULT

• Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2003 Jan;160(1):13-23. doi: 10.1176/appi.ajp.160.1.13.

  PMID: 12505794 RESULT

• Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature. 2006 Aug 31;442(7106):1042-5. doi: 10.1038/nature05051. Epub 2006 Aug 23.

  PMID: 16929307 RESULT

MeSH Terms

Interventions

Levodopa; Haloperidol

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Butyrophenones; Ketones

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo x Haloperidol x LDOPA

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: November 27, 2018
• Study Start: June 1, 2017
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: October 10, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)