Evaluation of the effect of a single dose of psilocybin on neural correlates of cognitive control in patients with CNEP (psychogenic nonepileptic seizures): a single-arm, open-label pilot study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

5 Nov 2024 → ongoing

Decision date (initial)

2024-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU DE NIMES

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To assess by functional brain MRI the effect of psilocybin on the activity of brain regions associated with cognitive control during an emotional Go-No Go task in patients with CNEP.

Secondary objectives 8

1. To evaluate by functional brain MRI the effect of psilocybin on the resting activity of regions involved in cognitive control in patients suffering from CNEP.
2. To evaluate by functional brain MRI the effect of psilocybin on the resting activity of the default mode network (DMN) in patients with CNEP.
3. To assess the effect of psilocybin on improving cognitive control abilities during an emotional Go-No Go task by analysis of error rate (%) and response latency (ms) in patients with CNEP.
4. To assess the effect of psilocybin on improving cognitive control abilities during a neutral Go-No Go task by analysis of error rate (%) and response latency (ms) in patients with CNEP.
5. Evaluate the effect of psilocybin on the frequency of CNEP.
6. Evaluate the effect of psilocybin on the functional impact of CNEP up to 3 months after administration.
7. To assess the effect of psilocybin on dissociative symptoms using the DES scale up to 3 months after administration in patients suffering from CNEP.
8. Assess the psychic tolerance of psilocybin using the 5D-ASC scale up to 3 months after administration in patients suffering from CNEP

Conditions and MedDRA coding

psychogenic non-epileptic seizures

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Euthymic patient according to the MINI questionnaire.
2. Patient able to speak and understand French.
3. Diagnosis of CNEP confirmed by video-EEG, evolving for more than 3 months and meeting DSM-5 criteria.
4. Normal brain MRI during initial evaluation as part of routine care
5. Patient who has signed the consent form.
6. Patient affiliated or beneficiary of a health insurance plan.
7. Adult patient (≥18 years) and under 60 years of age (<).
8. Patient available for 6-month follow-up.
9. Good physical health and absence of unstable medical pathology. These pathologies include cardiovascular comorbidities: history of stroke, myocardial infarction, heart failure, arrhythmia, uncontrolled hypertension (greater than 165/95 mmHg at screening); organic epileptic syndrome and active neurological comorbidities; endocrine pathologies (dysthyroidism and adrenal insufficiency, type I diabetes or insulin-requiring type II diabetes, history of severe hypoglycemia requiring hospital treatment); significant impairment of liver function; glaucoma; symptomatic prostate hypertrophy or bladder neck obstruction.
10. Patients receiving SSRI (Selective Serotonin Reuptake Inhibitor) or SNRI (Serotonin and Noradrenaline Reuptake Inhibitor) antidepressant therapy may continue to do so for the duration of the trial, without modification. Other psychotropic treatments will not be interrupted.

Exclusion criteria 23

1. Severe risk of suicide in the opinion of the clinician.
2. Medical conditions that would preclude safe participation in the trial; for example: Significant impairment of liver function, coronary artery disease, history of arrhythmia, heart failure, uncontrolled hypertension (greater than 165/95 mmHg at screening), history of stroke, severe asthma, hyperthyroidism, narrow angle glaucoma, uncontrolled type I or type II diabetes or a history of ketoacidosis, hyperglycaemic coma or severe hypoglycaemia with loss of consciousness.
3. Women who are pregnant or breastfeeding, or who intend to become pregnant during the study.
4. Insufficient contraception.
5. Contraindications to magnetic resonance imaging.
6. Allergy, hypersensitivity or other adverse reaction to previous use of psilocybin or other hallucinogens.
7. Use of hallucinogenic substances (excluding cannabis) more than 10 times in the course of a lifetime or in the last two months, irrespective of frequency.
8. Use of medication likely to interfere with the effects of psychedelics.
9. Regular consumption of alcoholic beverages (>20 drinks/week).
10. Patient participating in an interventional drug study.
11. Patients in a period of exclusion determined by another study.
12. High risk of adverse emotional or behavioural reaction according to the investigator's clinical assessment (e.g. severe personality disorder, antisocial behaviour, severe current stressors, lack of significant social support).
13. Patient under court protection, guardianship or curatorship.
14. Patient unable to give consent.
15. Patients for whom it is impossible to provide informed information.
16. Active dependence on a substance according to the MINI questionnaire (excluding tobacco).
17. Psychotropic treatment (anxiolytics, antipsychotics, hypnotics) modified in the last month.
18. Patient suffering from intellectual disability.
19. Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder or psychosis not otherwise specified.
20. Family history of schizophrenia, schizoaffective disorder or type 1 bipolar disorder in first- or second-degree relatives.
21. Any unstable disease or physical condition determined by history or laboratory tests (ECG, blood tests at inclusion). These conditions include cardiovascular co-morbidities: history of stroke, myocardial infarction, heart failure, arrhythmia, uncontrolled hypertension (greater than 165/95 mmHg at screening; organic epileptic syndrome and active neurological comorbidities; endocrine pathologies (dysthyroidism and adrenal insufficiency, type I diabetes or insulin-requiring type II diabetes, history of severe hypoglycaemia requiring hospital treatment); significant impairment of liver function; glaucoma; symptomatic prostatic hypertrophy or bladder neck obstruction.
22. Presence of neurological co-morbidities.
23. Patient on antidepressant treatment other than SSRIs or SNRIs. (Antidepressant treatments other than SSRIs or SNRIs are prohibited in the trial. Patients receiving antidepressant treatment of a different class (MAOIs, tricyclics, tetracyclics), alone or in combination, will not be included in the study).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Quantification of changes in the activity of the cognitive control network on functional brain MRI during an emotional Go-No Go task (described by Fauvé et al. (2022)) performed before (D-3) and after (D+5) psilocybin administration

Secondary endpoints 8

1. Changes in brain activity on resting-state functional brain MRI of the cognitive control network before (D-3) and after (D+5) psilocybin administration.
2. Changes in brain activity on resting-state MRI of the Default-Mode Network (DMN) before (D-3) and after (D+5) psilocybin administration.
3. Collection of the number of errors (n) and measurement of response latency (ms) during an emotional Go-No Go task before (D-3) and after (D+5) psilocybin administration.
4. Collection of the number of errors (n) and measurement of response latency (ms) during a neutral Go-No Go task before (D-3) and after (D+5) psilocybin administration.
5. Measurement of the frequency of CNEP in the 6 weeks before and after psilocybin administration using a seizure diary.
6. Measurement of changes in the CGI-CNEP scale before (D-3) and after (D+5, M1 and M3) psilocybin administration; scoring by the neurologist and psychiatrist.
7. Measurement of changes in dissociative symptomatology using the DES scale before (D-45, D-3) and after (D+5, M1 and M3) psilocybin administration.
8. Administration of the 5D-ASC (5-Dimensional Altered States of Consciousness Questionnaire) at D0 then D+5, M1 and M3 after psilocybin administration..

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

Place Du Professeur Robert Debre

City

Nimes

Postcode

30900

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

leonie gazel

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

leonie gazel

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications