Noradrenaline, Acetylcholine and Dynamic Learning in Healthy Humans

NCT03957174 | Completed

• 1 other identifier: R62807/RE001
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to characterize the role of central norepinephrine and acetylcholine on reward and emotion related information processing in healthy volunteers using behavioural tasks and pupillometry (with eye tracking equipment). The pharmacological compounds used in the study (reboxetine and rivastigmine) are used as tools to manipulate these systems rather than to treat patients. The aim of the study is not to study the clinical effects, pharmacodynamics, adverse reactions, absorption, distribution, metabolism or excretion of the drugs. Further, the population studied is non-clinical, the drugs are not administered in a therapeutic dosing regimen (only a single dose of study drug will be administered) and the investigators do not measure clinically significant outcomes.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Change in learning rates

  Learning rates from negative and positive outcomes received in a reinforcement learning task

  2 hours after dosing (NB outcome is the change from the baseline measure to this time point)

Secondary Outcomes (2)

• Pupil size

  2 hours after dosing (NB outcome is the change from the baseline measure to this time point)

• Affective processing

  2 hours after dose

Study Arms (3)

Reboxetine

EXPERIMENTAL

Single dose of 4mg

Drug: Reboxetine

Rivastigmine

EXPERIMENTAL

Single dose of 3mg

Drug: Rivastigmine

Placebo

PLACEBO COMPARATOR

Single dose of placebo

Drug: Placebo oral tablet

Interventions

Reboxetine DRUG

Single dose used to increase central norepinepherine

Reboxetine

Rivastigmine DRUG

Single dose to increase central acetylcholine

Rivastigmine

Placebo oral tablet DRUG

Single dose as control condition

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 on the day of the study

You may not qualify if:

• Current or past psychiatric disorder (e.g. depression, bipolar disorder etc.)
• BMI outside of range 187.5 and 2530
• Any severe medical condition not stabilized at the time of the experiment that, in the opinion of the study medic, would compromise the safety or conduct of the study including significant hypertension (diastolic pressure \> 100mmHg) or bradycardia (pulse less than 50 bpm).
• Any history of seizures, glaucoma or pancreatitis
• 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 month) 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.)
• Harmful alcohol use in the last 6 months (harmful alcohol use established based on self-reported work-related or social problems due to alcohol use or other's feedback to the participant that s/he should cut down)
• History of allergic reactions to relevant substances (reboxetine, rivastigmine)
• Previous participation in a study using the same or similar tasks
• In the researcher's or study medic'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

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

Reboxetine; Rivastigmine

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Overencapsulated drug/placebo capsule used. Investigator and participant blind to allocation. Randomisation schedule drawn up by independent researcher and kept in locked cabinet.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three group parallel design

Study Record Dates

• First Submitted: May 10, 2019
• First Posted: May 21, 2019
• Study Start: June 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: June 16, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: After completion of data analysis, and then indefinitely.
• Access Criteria: Researchers who contact the PI with a valid interest in the data (as assessed by the PI)

Locations

GB (1)