LearningPhase 4DOREANCT07267559
Dual Orexin Antagonism and Emotion and Affective Processing Study
A Phase 4 study testing Daridorexant 50 mg in people with Learning and Cognitive Functioning, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Learning, Cognitive Functioning, Emotional Processing
- What is being tested?
- Daridorexant 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2025to 1 Oct 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 26Show fewer
- 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.
- Smoking more than 5 cigarettes per day (or other nicotine replacement equivalent, including vaping on average more than 50 puffs a day).
- 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.
- 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)
- Inability to ingest up to 95mg of lactose.
- Previous participation in any other drug study or sleep intervention study in the last three months.
- 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
- Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Department of Psychiatry, University of Oxford
Oxford, OX3 7JX
Michael J Colwell, DPhil, 01865 618200 ext. +44, michael.colwell@psych.ox.ac.uk
Daniela A Borges, MD, 01865 618200 ext. +44, daniela.almeidaborges@psych.ox.ac.uk
About this study
Official title: 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.
- Conditions
- Learning, Cognitive Functioning, Emotional Processing
- Being tested
- Daridorexant 50 mg, Placebo
- Keywords
- Drug, Orexin, Hypocretin, Healthy volunteers, Learning, Cognition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daridorexant 50 mgDrug
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.
PlaceboOther
Lactose film-coated tablet will be encapsulated in an opaque capsule (identical to the experimental arm drug).
| Study group | Role | What they receive |
|---|---|---|
| Daridorexant | Experimental | Acute daridorexant (50mg) Receives: Drug: Daridorexant 50 mg |
| Placebo | Placebo comparator | Inactive placebo comparator Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pavlovian Aversive Learning Task Computational Parameter Estimates
Change in the participant-specific parameter estimates produced by task model fitting.
Measured: 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.
Measured: 1-2 hours after single dose of drug or placebo.
Secondary outcomes (10)
Pupilometry during Pavlovian Aversive Learning Task
Changes in pupil size (dilation or constriction) in response to task stimuli
Measured: 1-2 hours after single dose of drug or placebo.
Pupilometry during Affective Go/No-Go Task
Changes in pupil size (dilation or constriction) in response to task stimuli.
Measured: 1-2 hours after single dose of drug or placebo.
Salivary Alpha Amylase Levels
Changes in Salivary Alpha Amylase Levels before, during and after Pavlovian Aversive Learning Task
Measured: 1-2 hours after single dose of drug or placebo.
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT)
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT) in drug group compared with the placebo group
Measured: 2-3 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task
Accuracy of target selection on the Colour Change Detection Task in pilosant group compared with the placebo group.
Measured: 2-3 hours after single dose of drug or placebo.
Accuracy of emotional labeling of facial expressions during the facial emotion recognition task
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
Measured: 2-3 hours after single dose of drug or placebo.
Accuracy during categorisation of emotional words
Accuracy to categorise positive and negative descriptor words
Measured: 2-3 hours after single dose of drug or placebo.
Accuracy during recall of emotional words
Number of words accurately recalled
Measured: 2-3 hours after single dose of drug or placebo.
Pavlovian Aversive Learning Task Behavioural Performance
Change in behavioural performance (response time; accuracy)
Measured: 1-2 hours after single dose of drug or placebo.
Affective Go/No-Go Task Behavioural Performance
Change in behavioural performance (response time; accuracy)
Measured: 1-2 hours after single dose of drug or placebo.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2025
- Study start1 Oct 2025
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LearningStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine J Harmer, DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07267559
- Sponsor's protocol ID
- DOREA
- Acronym
- DOREA
- Status last verified
- Oct 2025
- First submitted
- 14 Nov 2025
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigation of the Effects of Dual Orexin Antagonism on Emotional Processing and Learning in Healthy Individuals
- ClinicalTrials.gov ID
- NCT07267559
- Acronym / sponsor ID
- DOREA / DOREA
- Conditions
- Learning, Cognitive Functioning, Emotional Processing
- Keywords
- Drug, Orexin, Hypocretin, Healthy volunteers, Learning, Cognition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 5 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Daridorexant | Experimental | Drug: Daridorexant 50 mgAcute daridorexant (50mg) |
| Placebo | Placebo comparator | Other: PlaceboInactive placebo comparator |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (26 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daridorexant 50 mgAcute (single dose) daridorexant encapsulated in an opaque capsule. Oral administration. Daridorexant (brand name Quviviq) is FDA-approved for the treatment of insomnia in adults. | Drug | Daridorexant |
| PlaceboLactose film-coated tablet will be encapsulated in an opaque capsule (identical to the experimental arm drug). | Other | Placebo |
Primary outcome
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.
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.
10 secondary outcomes
Pupilometry during Pavlovian Aversive Learning Task
Time frame: 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.
Salivary Alpha Amylase Levels
Time frame: 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.
Accuracy of target selection on the Colour Change Detection Task
Time frame: 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 during categorisation of emotional words
Time frame: 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.
Pavlovian Aversive Learning Task Behavioural Performance
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Catherine J Harmer, DPhil principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Daridorexant 50 mg in people with Learning and Cognitive Functioning, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael J Colwell, DPhil (01865 618200 ext. +44, michael.colwell@psych.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pavlovian Aversive Learning Task Computational Parameter Estimates (time frame: 1-2 hours after single dose of drug or placebo.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.