Psilocybin for Stable ischemic heart disease

Inclusion criteria

• {"criterion_text":"- Men and women aged 18-80.\n- Diagnosis of stable ischemic heart disease (I25.9).\n- A coronary finding of stenosis on one of the major coronary arteries of at least 2.5 mm in diameter with narrowing that does not exceed 50 % of the reference diameter and is on the native artery without previous intervention.\n- Patient's cognitive ability to fully understand CT information and study questionnaires.\n- Participants of childbearing age or with preserved fertility must agree to use prescribed contraceptive methods throughout the clinical trial..The following methods of contraception are required: (a) Women - we require at least one of the highly effective conception protection methods listed below: Combined (estrogen and progesterone) hormonal contraceptives (oral, transdermal, or intravaginal); Progesterone hormonal contraceptives (oral, transdermal, or intravaginal); Intrauterine device (IUD); Intrauterine Hormone Releasing System (IUS); Bilateral fallopian tube closure; Bilateral interruption of fallopian tubes in a partner; Sexual abstinence. (b) Men - use of at least an adequate barrier contraceptive method (condom) or sexual abstinence from the signing of the informed consent until 48 hours after administration of the study medication (study visit F4)."}

Exclusion criteria

• {"criterion_text":"- Severe neurological disease of the CNS. In case of suspicion of such disease, the CNS imaging (CT/MR) must be negative.\n- Hepatic dysfunction with GGT, AST, ALT values > 5 times the upper limit of normal, total bilirubin > 50 μmol/l\n- Cardiovascular instability in the sense of uncorrected hypertension (baseline BP ≥ 140/95 mm Hg - mean of 3 measurements), manifest heart failure NYHA II or more, left ventricular ejection fraction < 50%, history of ventricular tachycardia except reperfusion arrhythmias, atrial fibrillation with resting ventricular rate > 100 beats/min (mean of 3 measurements)\n- Severe thrombocytopenia < 50 x 10^9/l, resistant to replacement\n- Anatomical findings not allowing IVUS and OCT examination. i.e. tortuous coronary artery, markedly calcified stenosis.\n- Myasthenia gravis\n- Epilepsy including a history of isolated epileptic seizures\n- Known paraneoplastic syndrome or ectopic hormone production by the primary tumour, which could include hypercalcemia, Cushing's syndrome, hypoglycaemia, SIADH, or carcinoid syndrome.\n- Sleep apnoea syndrome\n- Status post aortocoronary bypass with a functional graft to the artery of interest\n- Diabetes mellitus on insulin or corrected with oral antidiabetic agents if there is a history of clinically significant hypoglycaemia.\n- Any other serious psychiatric illness based on psychiatric examination\n- Prior myocardial infarction less than 6 weeks ago with full revascularization\n- Prior stroke and/or TIA less than 6 months ago\n- Clinically significant peripheral vascular disease (acute venous thrombosis, chronic venous insufficiency at the stage of tibial ulceration, lower extremity ischemic disease at the stage of defects)\n- Focal neurological findings\n- Pulmonary disease with a reduction in vital capacity to lower than 75% of appropriate values, or FEV1 < 1,5 l\n- Psychoterapy initiated less than 3 months prior to the start of the RAFAEL study\n- Patient's condition does not allow compliance with concomitant therapy\n- Inability to orally administer study medication in capsule form\n- Untreated or incompletely compensated hyperthyroidism\n- Use of psilocybin or another serotonergic psychedelic in the past 12 months\n- Stable treatment with antidepressants / thymostabilisers / antipsychotics in a non-hypnotic indication (doses must not achieve the antidepressant, antipsychotic or thymostabilising effect as per SPC).\n- Any current or history of psychotic illness from the diagnosis F2X.X\n- Renal insufficiency with creatinine clearance < 0.6 ml/s\n- Presence of suicidal ideation or suicidal behavior based on the C-SSRS version Lifetime/Recent (L/R) or C-SSRS version since last visit (SLV), specifically, a \"yes\" response to question 4 and 5 in the past 6 months and/or any \"yes\" response to suicidal behavior questions in the past 6 months and/or clinical examination\n- Current or history of alcohol or drug dependence F1X.X. unless at least 2 years of abstinence can be demonstrated\n- Other inappropriateness of the patient's classification based on the clinical judgment of the examining physician\n- Known intolerance or allergy to psilocybin or midazolam\n- Pregnancy or breastfeeding"}

Primary endpoints

• {"endpoint_text":"- Change in the atherosclerotic plaque volume between the baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days ± 28 days after IMP administration (F4) measured with intravascular ultrasound (IVUS).","definition_or_measurement_approach":"Measured with intravascular ultrasound (IVUS) between baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days ± 28 days after IMP administration (F4)."}

Secondary endpoints

• {"endpoint_text":"- Change in the composition of atherosclerotic plaques between the baseline (F2) and follow-up invasive coronary artery examination (F7) 365 days ± 28 days after IMP administration (F4)","definition_or_measurement_approach":"Assessment of plaque composition between baseline (F2) and follow-up invasive coronary artery examination (F7) at 365 days ± 28 days after IMP administration (F4)."}
• {"endpoint_text":"- Reduction in the incidence of the thin-cap fibroatheroma (TCFA), between the baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days ± 28 days after IMP administration (F4)","definition_or_measurement_approach":"Incidence of thin-cap fibroatheroma (TCFA) assessed between baseline (F2) and follow-up (F7) at 365 days ± 28 days after IMP administration (F4)."}
• {"endpoint_text":"- Change in the increase of the in fibrous cap thickness measured with optical coherence tomography between the baseline (F2) and follow-up invasive coronary artery examination (F7) 365 days ± 28 days after IMP administration (F4)","definition_or_measurement_approach":"Increase in fibrous cap thickness measured using optical coherence tomography (OCT) between baseline (F2) and follow-up (F7) at 365 days ± 28 days after IMP administration (F4)."}
• {"endpoint_text":"- Safety evaluation (blood pressure, heart rate) of study medication","definition_or_measurement_approach":"Safety assessments including blood pressure and heart rate measurements during study medication exposure and follow-up."}

Czechia

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

515

Number Of Sites

2

Number Of Participants

60

Primary sponsor

Full Name

Psyon s.r.o.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Czechia

Third parties

• {"country":"Czechia","full_name":"Twma s.r.o.","duties_or_roles":"sponsorDuties codes: 1, 12 (as listed in CTIS thirdParty entry)","organisation_type":"Pharmaceutical company"}