Clinical trial NCT06258031: PsilOCD: A Pharmacological-Challenge Feasibility Study
Official title: PsilOCD: Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity (A Pharmacological-Challenge Feasibility Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2024-02-14
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Two different, fixed doses of psilocybin (Dose A = 10mg - x, Dose B = 10mg - y) are given on two separate dosing days to all patients.
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the impact of psilocybin on cognitive inflexibility and neural plasticity in a cohort of people with obsessive-compulsive disorder (OCD).

Detailed description: This mechanistic study will utilise a within-subjects design, administering up to 10mg of psilocybin to participants with OCD (DSM-5 criteria) on two separate instances spaced four weeks apart. To ensure consistency and participant safety, dosing will occur under medical supervision with psychological support from two experienced therapists. Before and after each session, participants will engage in virtual preparation and integration sessions led by their therapists. Cognitive tasks will be administered in the days following each dosing session. Additionally, acute post-dosing EEG recordings will be conducted, and blood samples will be taken after each dosing session. OCD symptoms will also be assessed seven times throughout the trial by an external blinded psychiatrist, serving as a secondary outcome. Collectively, these measures aim to evaluate changes in cognitive inflexibility, decision-making abilities, neuroplasticity (peripheral blood markers and EEG measures), inflammation (peripheral blood markers), and symptomatology following each dosing session.

Eligibility criteria: Key Inclusion Criteria:

* Aged 20 to 65 years;
* Any gender;
* A primary diagnosis of OCD (based on the Mini-International Neuropsychiatric Interview (M.I.N.I.));
* Has met diagnostic criteria for OCD for at least 12 months;
* Willing to comply with protocol and associated lifestyle restrictions;
* Adequate understanding of the English language to give informed consent and participate in the study;
* Participant can attend visits as an outpatient;
* Comfortable using a computer, access to internet from home, and willing to participate in some of the study visits via video-link.

Key Exclusion Criteria:

* Current or past history of dependent (according to ICD10 criteria) substance use (not including nicotine and/or caffeine), Tourette's syndrome, autism spectrum disorder, epilepsy, organic mental disorder, or a personality disorder apart from obsessive-compulsive personality disorder;
* Current or past history of psychosis or mania in themselves or a first-degree relative;
* Unstable physical health;
* Significantly abnormal clinical test result;
* Heavy smoker, or unable to attend the dosing days (including the subsequent recovery part) without a smoking break;
* Unwillingness to allow their GP or mental health practitioners to be informed of their participation (or, to allow study team access to Summary Care Record).

Primary outcomes:
measure: Intradimensional-extradimensional (ID-ED) set shift
timeFrame: 4 weeks
measure: The visual long-term potentiation (vLTP) electroencephalogram (EEG) paradigm (acute quantified changes in neuroplasticity in the visual system).
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical measures of compulsivity of relevance to OCD including Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
timeFrame: 8 weeks
measure: Cognitive measure: Reversal learning task (administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB))
timeFrame: 4 weeks
measure: Cognitive measure: Information-seeking task
timeFrame: 4 weeks
measure: Cognitive measure: Visuospatial memory paired-associates learning task (administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB))
timeFrame: 4 weeks
measure: Measures of the acute psychological effects of psilocybin including the Emotional Breakthrough Inventory
timeFrame: 4 weeks
measure: Measures of depression symptoms including the Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: 8 weeks
measure: Measures of anxiety symptoms including the State-Trait Anxiety Inventory (STAI)
timeFrame: 8 weeks
measure: Acute plasma serum concentration of Brain-Derived Neurotrophic Factor (BDNF)
timeFrame: 4 weeks
measure: Oura: heart-rate variability
timeFrame: 8 weeks
measure: Oura: sleep stages
timeFrame: 8 weeks
measure: Oura: REM sleep
timeFrame: 4 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: CIPPRes Clinic
Study officials:
affiliation: Imperial College London
name: Professor David Nutt
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Dr David Erritzoe
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hertfordshire/Imperial College London
name: Dr Luca Pellegrini
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hertfordshire
name: Professor Naomi Fineberg
role: PRINCIPAL_INVESTIGATOR
References: