PSILOCYBINE for Psychogenic non-epileptic seizures

Inclusion criteria

• {"criterion_text":"- Euthymic patient according to the MINI questionnaire.\n- 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.\n- Patient able to speak and understand French.\n- Diagnosis of CNEP confirmed by video-EEG, evolving for more than 3 months and meeting DSM-5 criteria.\n- Normal brain MRI during initial evaluation as part of routine care\n- Patient who has signed the consent form.\n- Patient affiliated or beneficiary of a health insurance plan.\n- Adult patient (≥18 years) and under 60 years of age (<).\n- Patient available for 6-month follow-up.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Severe risk of suicide in the opinion of the clinician.\n- Patient participating in an interventional drug study.\n- Patients in a period of exclusion determined by another study.\n- 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).\n- Patient under court protection, guardianship or curatorship.\n- Patient unable to give consent.\n- Patients for whom it is impossible to provide informed information.\n- Active dependence on a substance according to the MINI questionnaire (excluding tobacco).\n- Psychotropic treatment (anxiolytics, antipsychotics, hypnotics) modified in the last month.\n- Patient suffering from intellectual disability.\n- Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder or psychosis not otherwise specified.\n- 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.\n- Family history of schizophrenia, schizoaffective disorder or type 1 bipolar disorder in first- or second-degree relatives.\n- 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.\n- Presence of neurological co-morbidities.\n- 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).\n- Women who are pregnant or breastfeeding, or who intend to become pregnant during the study.\n- Insufficient contraception.\n- Contraindications to magnetic resonance imaging.\n- Allergy, hypersensitivity or other adverse reaction to previous use of psilocybin or other hallucinogens.\n- 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.\n- Use of medication likely to interfere with the effects of psychedelics.\n- Regular consumption of alcoholic beverages (>20 drinks/week)."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measurement by functional brain MRI during an emotional Go-No Go task, performed at baseline (D-3) and after treatment (D+5); outcome is quantification of changes in activity of the cognitive control network."}

Secondary endpoints

• {"endpoint_text":"- Changes in brain activity on resting-state functional brain MRI of the cognitive control network before (D-3) and after (D+5) psilocybin administration.","definition_or_measurement_approach":"Resting-state functional brain MRI at baseline (D-3) and post-treatment (D+5) assessing changes in activity of the cognitive control network."}
• {"endpoint_text":"- Changes in brain activity on resting-state MRI of the Default-Mode Network (DMN) before (D-3) and after (D+5) psilocybin administration.","definition_or_measurement_approach":"Resting-state MRI at baseline (D-3) and post-treatment (D+5) assessing DMN activity changes."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Behavioral metrics collected during emotional Go-No Go task at D-3 and D+5: number of errors (n) and response latency (ms)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Behavioral metrics collected during neutral Go-No Go task at D-3 and D+5: number of errors (n) and response latency (ms)."}
• {"endpoint_text":"- Measurement of the frequency of CNEP in the 6 weeks before and after psilocybin administration using a seizure diary.","definition_or_measurement_approach":"Seizure diary used to record frequency of CNEP during the 6 weeks before and 6 weeks after administration."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"CGI-CNEP scale administered at D-3, D+5, M1 and M3; scored by neurologist and psychiatrist to assess changes."}
• {"endpoint_text":"- Measurement of changes in dissociative symptomatology using the DES scale before (D-45, D-3) and after (D+5, M1 and M3) psilocybin administration.","definition_or_measurement_approach":"DES scale administered at D-45, D-3, D+5, M1 and M3 to measure dissociative symptoms over time."}
• {"endpoint_text":"- Administration of the 5D-ASC (5-Dimensional Altered States of Consciousness Questionnaire) at D0 then D+5, M1 and M3 after psilocybin administration..","definition_or_measurement_approach":"5D-ASC questionnaire administered at D0, D+5, M1 and M3 to assess altered states of consciousness."}

France

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

13-01-2025

Processing Time Days

279

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Nimes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France