Study of the Effects of Atomoxetine on Motivation

NCT07771595 | Not Yet Recruiting Phase 4

• 1 other identifier: MS IDREC 2605385
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates how increasing noradrenaline levels with atomoxetine affects motivation and information processing relevant to apathy. Apathy, characterised by low motivation and reduced goal-directed behaviour, is common across neuropsychiatric disorders and is associated with poorer outcomes. Atomoxetine, a noradrenaline reuptake inhibitor, has been shown to influence effort, reward learning, and decision-making; however, its effects on cognitive processes relevant to apathy remain unclear. This study will investigate how pharmacologically increasing noradrenaline levels with atomoxetine affects different components of motivation altered in apathy, including reward processing, effort-based decision-making, goal-directed behaviour, and learning. In a within-subject, double-blind, placebo-controlled, randomised study, forty healthy participants with varying levels of apathy will complete a computerised task battery after receiving a single dose of atomoxetine (40 mg) and placebo. Validated tasks assessing motivation, reward learning, decision-making, goal-directed behaviour, and information processing will be used to examine whether and how atomoxetine influences motivation-related cognitive processes.

Conditions

Apathy

Keywords

Atomoxetine; Apathy; Motivation; Reward Processing

Outcome Measures

Primary Outcomes (2)

• Effort-based choice behaviour during the Apple Gathering Task

  Change in the acceptance rate of offers requiring varying levels of physical effort for reward, measured during the Apple Gathering Task. Higher acceptance rates indicate greater willingness to exert effort for reward.

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.

• Effort-based choice behaviour during the Mental Effort Task

  Change in the acceptance rate of offers requiring varying levels of cognitive effort for reward, measured during the Mental Effort Task. Higher acceptance rates indicate greater willingness to exert cognitive effort for reward.

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo

Secondary Outcomes (6)

• Prior goal precision on the Goal Priors Assay Task

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.

• Reinforcement learning under working memory load task behavioural performance

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.

• Reinforcement learning under working memory load task parameter estimate

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.

• Affective Go/No-Go Task Behavioural Performance

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.

• Reward sensitivity computational parameter estimates from effort-based decision-making tasks.

  During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo.

Study Arms (2)

Sequence A: Atomoxetine → Placebo

EXPERIMENTAL

Participants receive a single dose of atomoxetine (40 mg) at visit 1 and placebo at visit 2.

Drug: Atomoxetine; Other: Placebo

Sequence B: Placebo → Atomoxetine

EXPERIMENTAL

Participants receive a single dose of placebo at visit 1 and atomoxetine (40 mg) at visit 2.

Drug: Atomoxetine; Other: Placebo

Interventions

Placebo OTHER

Sucrose pillules will be encapsulated in an opaque capsule (identical to the experimental drug).

Sequence A: Atomoxetine → Placebo; Sequence B: Placebo → Atomoxetine

Atomoxetine DRUG

Acute (single dose) of Atomoxetine (40mg). Oral administration. Atomoxetine is FDA approved for the treatment of ADHD in adults and children.

Sequence A: Atomoxetine → Placebo; Sequence B: Placebo → Atomoxetine

Eligibility Criteria

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

You may qualify if:

• Age: 18-45
• Good physical health
• Willing and able to give informed consent to participate in the study
• Sufficient knowledge of English language to understand and complete the study tasks

You may not qualify if:

• Current DSM-5 axis-I diagnosis (based on SCID results at screening) or history of a severe psychological disorder such as psychotic disorder, bipolar disorder, alcohol or substance abuse, or post-traumatic stress disorder
• Previous or current extended period of persistent thoughts about ending one's life (longer than 5 days) or previous suicide attempt
• Clinical diagnosis of attention deficit hyperactivity disorder (ADHD) or on the waiting list for assessment
• Any intake of CNS-medication in the last 6 weeks (including as part of another study)
• Any current intake of blood pressure or other heart medication, including beta blockers
• Any current or previous medical condition or medication intake (last month) of any medication that, in the opinion of the study medic, may interfere with the safety of the participant or the scientific integrity of the study.
• Severely underweight (BMI \<17) or very obese (BMI \>40), OR otherwise deemed unsuitable for the study due to weight-related concerns at the discretion of the study medic
• History of cardiovascular, cerebrovascular disease
• Breathing or lung-related illnesses, significant liver or kidney problems, or severe gastrointestinal conditions.
• High blood pressure (defined as repeated measurements of blood pressure where either the systolic or the diastolic blood pressure, or both, are at or above 140/90 mmHg (https://doi.org/10.1093/eurheartj/ehy339)
• History of recurrent rashes or history of allergic reactions to relevant substances (atomoxetine, placebo treatment)
• Significant physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging.
• History of palpitations with sudden onset and offset,
• History of fainting on exertion or in response to fright or loud noise
• Family history of sudden death in a first-degree relative under 40 years of age

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, OX3 7JX, United Kingdom

Location

MeSH Terms

Conditions

Lethargy

Interventions

Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Catherine J Harmer, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta M Radzikowska, MSc

CONTACT

+447933989912; marta.radzikowska@psych.ox.ac.uk

Eva Periche-Tomas, PhD

CONTACT

+441865 613128; eva.perichetomas@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In a within-subject, double-blind, placebo-controlled, randomised study, forty healthy participants with varying levels of apathy will complete a computerised task battery after receiving a single dose of atomoxetine (40 mg) and placebo. Participants will complete two visits, 21 to 30 days apart.

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 18, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: August 18, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: A few months after all data has been completed (ETA October 2027), unblinding has occurred (ETA November 2027), and all data analyses has been completed (ETA Jan 2029).
• Access Criteria: The data will be made publicly available. Access requests will not be required.

Locations

GB (1)