Dual Orexin Antagonism and Emotion and Affective Processing Study

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• Pavlovian Aversive Learning Task Computational Parameter Estimates [Time frame: 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.]

Secondary outcome measures (10)

• 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.]

Eligibility criteria

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

• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Other

Study locations

United Kingdom · 1 center

• Department of Psychiatry, University of Oxford — Oxford

Identifiers

NCT: NCT07267559 · DOREA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗