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

University of Oxford

Status and phase: Enrolling; Phase 4

Conditions: Learning; Cognitive Functioning; Emotional Processing

Treatments: Other: Placebo; Drug: Daridorexant 50 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT07267559

DOREA

Details and patient eligibility

About

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.

Enrollment: 62 estimated patients

Sex: All

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adult participant, aged 18 to 30 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. 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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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62 participants in 2 patient groups, including a placebo group

Daridorexant

Experimental group

Description:

Acute daridorexant (50mg)

Treatment:

Drug: Daridorexant 50 mg

Placebo

Placebo Comparator group

Description:

Inactive placebo comparator

Treatment:

Other: Placebo