Ischemic Heart Disease
Conditions
Sponsors
Psyon, s.r.o.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Men and women aged 18-75 2) Diagnosis of stable coronary artery disease (I25.9) with a history of myocardial infarction at least 6 weeks before signing informed consent. 3) 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. 4) Patient's cognitive ability to fully understand CH information and study questionnaires. 5) Participants of childbearing age/preserved fertility must agree to use prescribed contraceptive methods and avoid pregnancy while exposed to study medication in this clinical trial. Since both psilocybin and midazolam are eliminated from the body within 24 hours, we are setting the minimum duration of contraceptive use at an interval from enrolment to three days after study drug administration. The following methods of contraception are required: (a) Females – we require proper use of at least a barrier contraceptive method (non-hormonal IUD and/or condom and/or vaginal pessary) or sexual abstinence. Hormonal contraception (combined hormonal contraception - in oral, vaginal or transdermal dosage form/ gestagen hormonal contraception combined with ovulation inhibition - in oral or injectable dosage form/ IUD) is not required but is accepted if the patient is already using) b) Men - use of at least an adequate barrier contraceptive method (condom) or sexual abstinence. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1) Severe neurological disease of the CNS. In case of suspicion of such disease, the CNS imaging (CT/MR) must be negative. 2) Focal neurological findings 3) Inability to orally administer study medication in capsule form 4) Patient's condition does not allow compliance with concomitant therapy (see sections 6.5 and 6.6) 5) Known intolerance or allergy to psilocybin or midazolam. 6) Pregnancy or breastfeeding 7) Hepatic dysfunction with GGT, AST, ALT values > 5 times the upper limit of normal, total bilirubin > 50 µmol/l 8) Cardiovascular instability in the sense of uncorrected hypertension (baseline BP = 140/90 mm Hg - mean of 3 measurements), manifest heart failure NYHA II or more, left ventricular ejection fraction 100/min (mean of 3 measurements) 9) Anatomical findings not allowing IVUS and OCT examination. I.e. tortuous coronary artery, markedly calcified stenosis 10) Status post aortocoronary bypass with a functional graft to the artery of interest 11) Prior myocardial infarction less than 6 weeks ago with full revascularization 12) Prior stroke and/or TIA less than 6 months ago 13) 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) 14) Pulmonary disease with a reduction in vital capacity to 75% of appropriate values, or FEV 1 less than 1.5 l. Sleep apnoea syndrome 15) Severe thrombocytopenia < 50 x 109/l, resistant to replacement 16) Myasthenia gravis 17) Epilepsy including a history of isolated epileptic seizures 18) Renal insufficiency with creatinine clearance < 0.6 ml/s 19) Known paraneoplastic syndrome or ectopic hormone production by the primary tumour, which could include hypercalcemia, Cushing's syndrome, hypoglycaemia, SIADH, or carcinoid syndrome 20) Diabetes mellitus on insulin or corrected with oral antidiabetic agents if there is a history of clinically significant hypoglycaemia 21) Glaucoma 22) Untreated or incompletely compensated hyperthyroidism 23) Use of psilocybin or another serotonergic psychedelic in the past 12 months 24) Any current or history of psychotic illness from the diagnosis F2x.x 25) Any other serious psychiatric illness based on psychiatric examination 26) Stable treatment with antidepressants/thymostabilisers/antipsychotics in a non-hypnotic indication (doses must not be above the antidepressant, antipsychotic or thymostabilising levels as per SPC). 27) Presence of suicidal ideation/behavior based on the C-SSRS version of the Lifetime/Recent (L/R) (specifically, a "yes" response to question 5 in the past 1 month and/or any "yes" response to suicidal behavior questions in the past 3 months) and/or clinical examination 28) Current or history of alcohol or drug dependence F1x.x. unless at least 2 years of abstinence can be demonstrated 29) Other inappropriateness of the patient's classification based on the clinical judgment of the examining physician
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate regression of atherosclerotic plaque volume (between baseline and follow-up invasive coronary artery disease examinations performed 12 months apart) in patients with coronary artery disease treated with standard hypolipidemic therapy to achieve target LDL cholesterol levels and randomized to psilocybin- or midazolam-assisted psychotherapy as a negative control. We expect that psilocybin-assisted psychotherapy will achieve regression at the upper range of published findings i.e. 3% reduction in plaque volume. ;Secondary Objective: - Change in the composition of atherosclerotic plaques between the initial and follow-up invasive coronary artery examination performed 12 months apart. - Reduction in the incidence of the highest-risk phenotype, thin-cap fibroatheroma (TCFA), between initial and follow-up invasive coronary artery angiography performed 12 months apart. - Use optical coherence tomography to measure the increase in fibrous cap thickness between baseline and follow-up invasive coronary artery angiography performed 12 months apart. We expect an increase in fibrous cap thickness when chronic inflammation is reduced, leading to the release of degradative enzymes from macrophages and thus the breakdown of fibrous tissue.;Primary end point(s): Evaluation of atherosclerotic plaque 12 months after psilocybin/midazolam potentiated psychotherapy using: •Selective coronarography •Intravascular ultrasound •Virtual histology •Optical Coherence Tomography (OCT) ;Timepoint(s) of evaluation of this end point: 12 months after psilocybin/midazolam potentiated psychotherapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in the composition of atherosclerotic plaques between the initial and follow-up invasive coronary artery examination performed 12 months apart. We hypothesize that the reduction of chronic stress during psilocybin potentiated psychotherapy will contribute to the chronic inflammatory process in the plaque and thus reduce necrotic tissue. - Reduction in the incidence of the highest-risk phenotype, thin-cap fibroatheroma (TCFA), between the initial and follow-up invasive coronary artery disease examinations performed 12 months apart - Using optical coherence tomography to measure the increase in fibrous cap thickness between initial and follow-up invasive coronary artery angiography performed 12 months apart We expect an increase in fibrous cap thickness when chronic inflammation is reduced, leading to the release of degradative enzymes from macrophages and thus the breakdown of fibrous tissue. ;Timepoint(s) of evaluation of this end point: 12 months after psilocybin/midazolam potentiated psychotherapy | — |
Countries
Czech Republic
Contacts
Public ContactPsyon – Psychedelická klinika
Psyon, s.r.o.
Outcome results
None listed