PsilOCD: A Pharmacological-Challenge Feasibility Study

Obsessive-Compulsive Disorder Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06258031
• Other study ID #: 298206
• Status: Recruiting
• Phase: Phase 1
• Start date: October 28, 2022
• Est. completion date: July 30, 2024

Study information

• Verified date: February 2024
• Source: Imperial College London
• Contact: Sorcha O'Connor
• Phone: +44 (0)20 7594 1074
• Email: s.oconnor22[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Obsessive-Compulsive Disorder

Intervention

Drug:
• Psilocybin (COMP360)
Up to 10mg on two occasions

Locations

Country	Name	City	State
United Kingdom	CIPPRes Clinic	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intradimensional-extradimensional (ID-ED) set shift	Scores on this neurocognitive task administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). ID-ED performance is an established measure of cognitive inflexibility in OCD (Chamberlain et al., Am J Psychiatry, 2007), with worse scores corresponding to decreased flexibility.	4 weeks
Primary	The visual long-term potentiation (vLTP) electroencephalogram (EEG) paradigm (acute quantified changes in neuroplasticity in the visual system).	We will assess acute changes in homosynaptic neuroplasticity using the visual long-term potentiation (vLYTP) EEG paradigm. In this paradigm, we induce neural plasticity in the occipital cortex by exposing participants to visual stimuli of varying frequencies. This task specifically quantifies homosynaptic plasticity because it triggers changes in neighbouring neurons within the occipital cortex.	8 weeks
Secondary	Clinical measures of compulsivity of relevance to OCD including Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Assess OCD symptoms over the study's duration (with higher scores corresponding to worse symptoms in all scales mentioned)	8 weeks
Secondary	Cognitive measure: Reversal learning task (administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB))	Assesses ability to adapt to changing contingencies; higher scores indicate better cognitive flexibility	4 weeks
Secondary	Cognitive measure: Information-seeking task	It tests participants' confidence and ability to make decisions involving uncertainty by monitoring their tendency to seek extra information (recently developed by Lion Schulz and colleagues, 2020)	4 weeks
Secondary	Cognitive measure: Visuospatial memory paired-associates learning task (administered as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB))	Serves as a control task; higher scores indicate better visuospatial memory faculties	4 weeks
Secondary	Measures of the acute psychological effects of psilocybin including the Emotional Breakthrough Inventory	Higher scores correspond to greater subjective emotional changes elicited by the acute psilocybin experience	4 weeks
Secondary	Measures of depression symptoms including the Montgomery-Åsberg Depression Rating Scale (MADRS)	Higher scores correspond to worse depressive symptoms	8 weeks
Secondary	Measures of anxiety symptoms including the State-Trait Anxiety Inventory (STAI)	Higher scores correspond to worse anxiety-related symptoms	8 weeks
Secondary	Acute plasma serum concentration of Brain-Derived Neurotrophic Factor (BDNF)	BDNF concentration (pg/mL) serves as a biomarker with significant functions in brain health, neuroplasticity, and the regulation of inflammation.	4 weeks
Secondary	Oura: heart-rate variability	Participants will be given an Oura ring to keep track of heart-rate variability (HRV) throughout the duration of the study (participants will not be able to see their own data).	8 weeks
Secondary	Oura: sleep stages	Oura rings will also measure the number of minutes/hours spent in each sleep stage (awake, light, deep, and rapid eye movement (REM))	8 weeks
Secondary	Oura: REM sleep	Examines acute changes in neuroplasticity. Participants detect subtle colour changes while listening to sound sequences, triggering an EEG signal increase in the auditory cortex. This measures the brain's ability to induce repetition suppression across consecutive trials, reflecting its capacity to adapt to expected sound sequences over time.	4 weeks