Dual Orexin Antagonism and Emotion and Affective Processing Study (DOREA)

March 16, 2026 updated by: University of Oxford

An Investigation of the Effects of Dual Orexin Antagonism on Emotional Processing and Learning in Healthy Individuals

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  1. History of, receiving or seeking treatment for any sleep or circadian rhythm disorder or positive in screening questionnaires.
  2. 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.

  3. 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
  4. 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.
  5. Body mass index (BMI) below 18 or above 30kg/m2.
  6. Current or past history of drug or alcohol dependency.
  7. 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.
  8. 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.
  9. Smoking more than 5 cigarettes per day (or other nicotine replacement equivalent, including vaping on average more than 50 puffs a day).
  10. Current or recent (past two months) use of any medication or medical devices (e.g. implanted neurostimulator) that affect brain function for the exception of contraceptives (pill, the Depo-Provera injection or the progesterone implant). This includes drugs that cause sedation (e.g. benzodiazepines, opioids, tricyclic antidepressants or sedative antipsychotics) or antihistamines.

  11. Current use of any medications at risk of interaction with daridorexant; in particular:

    • strong or moderate CYP3A inhibitors (e.g. strong inhibitors - itraconazole, clarithromycin, ritonavir, grapefruit juice; moderate inhibitors - fluconazole, verapamil, diltiazem, erythromycin, ciprofloxacin, cyclosporine)
    • strong or moderate CYP3A inducers (e.g. of strong inducers - rifampicin, carbamazepine, St. John's wort; moderate inducers - bosentan, efavirenz, etravirine, modafinil)
    • Gastric pH-modifiers (e.g. famotidine and proton pump inhibitors such as omeprazole)
    • P-gp transporters (e.g. dabigatran, digoxin)
  12. Inability to ingest up to 95mg of lactose.
  13. Previous participation in any other drug study or sleep intervention study in the last three months.
  14. Previous participation in any other study by the Psychopharmacology and Emotion Research lab (Department of Psychiatry, University of Oxford) or which uses the same computer tasks in the last 6 months
  15. Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Daridorexant
Acute daridorexant (50mg)
Drug: Daridorexant 50 mg
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.
Placebo Comparator: Placebo
Inactive placebo comparator
Other: Placebo
Lactose film-coated tablet will be encapsulated in an opaque capsule (identical to the experimental arm drug).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pavlovian Aversive Learning Task Computational Parameter Estimates
Time Frame: 1-2 hours after single dose of drug or placebo.
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
Time Frame: 1-2 hours after single dose of drug or placebo.
Change in the participant-specific parameter estimates produced by task model fitting.
1-2 hours after single dose of drug or placebo.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pupilometry during Pavlovian Aversive Learning Task
Time Frame: 1-2 hours after single dose of drug or placebo.
Changes in pupil size (dilation or constriction) in response to task stimuli
1-2 hours after single dose of drug or placebo.
Pupilometry during Affective Go/No-Go Task
Time Frame: 1-2 hours after single dose of drug or placebo.
Changes in pupil size (dilation or constriction) in response to task stimuli.
1-2 hours after single dose of drug or placebo.
Salivary Alpha Amylase Levels
Time Frame: 1-2 hours after single dose of drug or placebo.
Changes in Salivary Alpha Amylase Levels before, during and after Pavlovian Aversive Learning Task
1-2 hours after single dose of drug or placebo.
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT)
Time Frame: 2-3 hours after single dose of drug or placebo.
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT) in drug group compared with the placebo group
2-3 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task
Time Frame: 2-3 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task in pilosant group compared with the placebo group.
2-3 hours after single dose of drug or placebo.
Accuracy of emotional labeling of facial expressions during the facial emotion recognition task
Time Frame: 2-3 hours after single dose of drug or placebo.
Accuracy of emotion labels (e.g. disgusted face) assigned by participants to expressive faces during the facial emotion recognition task in drug group compared with the placebo group
2-3 hours after single dose of drug or placebo.
Accuracy during categorisation of emotional words
Time Frame: 2-3 hours after single dose of drug or placebo.
Accuracy to categorise positive and negative descriptor words
2-3 hours after single dose of drug or placebo.
Accuracy during recall of emotional words
Time Frame: 2-3 hours after single dose of drug or placebo.
Number of words accurately recalled
2-3 hours after single dose of drug or placebo.
Pavlovian Aversive Learning Task Behavioural Performance
Time Frame: 1-2 hours after single dose of drug or placebo.
Change in behavioural performance (response time; accuracy)
1-2 hours after single dose of drug or placebo.
Affective Go/No-Go Task Behavioural Performance
Time Frame: 1-2 hours after single dose of drug or placebo.
Change in behavioural performance (response time; accuracy)
1-2 hours after single dose of drug or placebo.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Oxford

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Catherine J Harmer, DPhil, University of Oxford

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 5, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DOREA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data which has been fully de-identified may be shared with other academic and commercial organisations in the future, including those outside of the UK and the EU. Participants will be informed of this and specific consent to this is obtained within the Informed Consent Form.

IPD Sharing 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).

IPD Sharing Access Criteria

The data will be made publicly available. Access requests will not be required.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • ANALYTIC_CODE

Study Data/Documents

  1. Study Protocol
  2. Informed Consent Form

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings