Dual Orexin Antagonism and Emotion and Affective Processing Study

NCT07267559 | Recruiting Phase 4

• 1 other identifier: DOREA
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators will examine the effects of blocking the orexin system on human behaviour and brain function using daridorexant, a medication that inhibits orexin activity. Orexin is a brain chemical involved in regulating sleep, emotion, motivation, and stress responses, which are often disrupted in mental health disorders. Healthy volunteers will be randomly assigned to receive a single dose of daridorexant or placebo in a double-blind design. Participants will then complete behavioural and cognitive tasks assessing emotional processing, aversive learning, and executive function. The study aims to clarify the role of orexin in emotional and cognitive processes relevant to conditions such as depression and anxiety.

Conditions

Learning; Emotional Processing; Cognitive Functioning

Keywords

Drug; Orexin; Hypocretin; Healthy volunteers; Learning; Cognition

Outcome Measures

Primary Outcomes (2)

• Pavlovian Aversive Learning Task Computational Parameter Estimates

  Change in the participant-specific parameter estimates produced by task model fitting.

  1-2 hours after single dose of drug or placebo.

• Affective Go/No-Go Task Computational Parameter Estimates

  Change in the participant-specific parameter estimates produced by task model fitting.

  1-2 hours after single dose of drug or placebo.

Secondary Outcomes (10)

• Pupilometry during Pavlovian Aversive Learning Task

  1-2 hours after single dose of drug or placebo.

• Pupilometry during Affective Go/No-Go Task

  1-2 hours after single dose of drug or placebo.

• Salivary Alpha Amylase Levels

  1-2 hours after single dose of drug or placebo.

• Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT)

  2-3 hours after single dose of drug or placebo.

• Accuracy of target selection on the Colour Change Detection Task

  2-3 hours after single dose of drug or placebo.

Study Arms (2)

Daridorexant

EXPERIMENTAL

Acute daridorexant (50mg)

Drug: Daridorexant 50 mg

Placebo

PLACEBO COMPARATOR

Inactive placebo comparator

Other: Placebo

Interventions

Daridorexant 50 mg DRUG

Acute (single dose) daridorexant encapsulated in an opaque capsule. Oral administration. Daridorexant (brand name Quviviq) is FDA-approved for the treatment of insomnia in adults.

Daridorexant

Placebo OTHER

Lactose film-coated tablet will be encapsulated in an opaque capsule (identical to the experimental arm drug).

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult participant, aged 18 to 40 years
• Willing and able to give informed consent for participation in the trial
• Able to follow study procedures as laid out in the participant information sheet
• Able to read and understand English
• Willing to avoid drinking alcohol, using recreational drugs, drinking grapefruit juice 24 hours before and after the study visit
• Willing to avoid driving or engaging in any activities requiring full alertness (e.g. cycling or operating heavy machinery) until the morning after the study visit day.
• Able to complete computer tasks without eye glasses even if uses correction regularly

You may not qualify if:

• History of, receiving or seeking treatment for any sleep or circadian rhythm disorder or positive in screening questionnaires.
• History of, receiving or seeking treatment for any clinically significant mental health condition (including but not limited to schizophrenia, psychosis, bipolar affective disorder, major depressive disorder, obsessive compulsive disorder, post-traumatic stress disorder) or positive in screening questionnaires.
• History of, or current medical condition(s) which might increase the risk of oral administration of daridorexant, including:
• ADHD requiring treatment with stimulants or other centrally-acting drugs
• Neurological problems, including traumatic brain injury, epilepsy, Central Nervous System tumours or other severe neurological problems (e.g. Parkinson's disease; blackouts requiring hospitalisation)
• Current Asthma, Chronic Obstructive Pulmonary Disease, emphysema or any medical condition that affects the lungs or breathing
• Mild to severe hepatic impairment (Child-Pugh class A-C)
• Severe renal disease
• Severe gastrointestinal problems
• History of, or current medical condition(s) which, in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study
• Pregnancy (as determined by urine pregnancy test taken during screening visit), intention to become pregnant or breastfeeding during the study or over the following six months.
• Body mass index (BMI) below 18 or above 30kg/m2.
• Current or past history of drug or alcohol dependency.
• Regular alcohol consumption of more than 21 units per week or use of recreational drugs or performance-enhancing drugs (e.g. cannabis, cocaine, amphetamines) within past three months.
• Excessive caffeine consumption, i.e., consumption higher than 400mg a day of caffeine. This corresponds to more than 4 cups of brewed coffee, 6 espressos or filtered coffees, 9 cups of black tea, 10 cans of cola, or two "energy shot" drinks.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, OX3 7JX, United Kingdom

RECRUITING

MeSH Terms

Interventions

daridorexant

Study Officials

• Catherine J Harmer, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael J Colwell, DPhil

CONTACT

01865 618200; michael.colwell@psych.ox.ac.uk

Daniela A Borges, MD

CONTACT

01865 618200; daniela.almeidaborges@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, Data Collectors, Outcomes Assessor
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to receive either daridorexant or placebo. Randomisation will be conducted using a variance minimisation procedure (Sella, Raz \& Cohen Kadosh, 2021) to balance baseline sleep chronotype and gender across groups. Each participant will receive a single oral dose of daridorexant (50 mg) or placebo, followed by pupillometry and cognitive/emotional assessments approximately one hour post-dose. The study aims to examine the effects of dual orexin antagonism on aversive learning and cognition, is not designed as an efficacy or safety trial.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 5, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 19, 2026

Record last verified: 2025-10

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 Oct 2026), unblinding has occurred (ETA Dec 2026), and all data analyses has been completed (Dec 2027).
• Access Criteria: The data will be made publicly available. Access requests will not be required.

Locations

GB (1)