Depressive disorder comorbid with cancer MedDRA version: 20.0 Level: PT Classification code 10012378 Term: Depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: Psilocybine
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Psilocybine
CAS Number: 520-52-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5
Sponsors
Národní ústav duševního zdraví
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Men and women aged 18-75 2) Diagnosis meeting the surgical diagnosis of the criteria for depressive syndrome (F41.2, F32.1, F32.2) comorbid with cancer, which: a) is at an advanced stage at the discretion of the referring oncologist / haematooncologist / internist / palliative doctor, or (b) has a poor prognosis (median survival of 5 years or less), or (c) is currently progressing; or (d) shows recurrence; or e) is in the phase of controlled disease, from the determination of oncological dg. at least 6 months have elapsed, but the patient still shows reactive depressive comorbidity. 3) From the point of view of antidepressant treatment, patients may be included who: a) have not used and do not regularly use any standard antidepressants (SSRIs, SNS, NaSSA, SARI, tricyclic and tetracyclic AD), b) they are currently taking standard antidepressants (SSRIs, SNRI NaSSA, SARI, tricyclic and tetracyclic AD) for at least 6 weeks in a stable dose, but the treatment has not provided them with a satisfactory mental state, c) underwent psychosocial interventions (counseling, psychotherapy, consultation of the support and palliative team ), but these interventions did not provide them with a satisfactory condition. 4) Cognitive fitness of the patient enabling a full understanding of information about CT and study questionnaires. 5) Each patient must have a secured caregiver (close, relative) who accompanies the patient on the 1st visit, picks up the patient on discharge after (each) Session with the substance (possibly after discharge from hospitalization) and will be in personal contact with the patient for at least 5 days a week. This caregiver must be available throughout the clinical trial. 6) Participants of childbearing potential / maintained fertility must agree to the use of prescribed contraceptive methods and prevent pregnancy during participation in a clinical trial: a) Women - we require the correct use of at least the barrier method of contraception (non-hormonal intrauterine device and / or condom and / or vaginal pessary) or sexual abstinence. No hormonal contraceptive is required (combined hormonal contraception - in oral, vaginal or transdermal dosage form / gestagen hormonal contraceptive associated with ovulation inhibition - in oral or injectable dosage form / intrauterine device), but is accepted if the patient is already taking it and is not contraindicated due to to oncological dg.) b) Men - use of an adequate at least 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1) Oncological disease with known invasion of the CNS or other serious CNS disease (except for asymptomatic CNS involvement in hematological diseases that have been treated with intrathecal cytostatics or radiotherapy) 2) Focal neurological findings 3) Impossibility of oral administration of study medication in the form of capsules 4) Expected survival time 5x upper limit of normal, total bilirubin> 50 µmol / l 9) Cardiovascular instability in terms of uncorrected hypertension (baseline BP = 140/90 mm Hg - mean value from 3 measurements), angina pectoris, heart failure or pre-existing clinically significant ECG changes (significant conversion disorders, significant arrhythmia) or tachycardia (baseline values ??= 100 beats - min - average value from 3 measurements) 10) Myocardial infarction less than 6 months ago 11) A stroke and / or TIA less than 6 months ago 12) Clinically significant peripheral vascular diseases (acute venous thrombosis, chronic venous insufficiency in the stage of shin ulcers, ischemic disease of the lower limbs in the stage of claudication) 13) Dyspnoea of ??any etiology higher than NYHA II, acute respiratory failure or severe respiratory insufficiency 14) Severe thrombocytopenia <30 x 109 / l, resistant to substitution 15) Myasthenia gravis 16) Epilepsy incl. history of isolated epileptic seizures 17) Renal insufficiency with GFR less than 0.66 ml / s / 1.73 m2 according to CKD-EPI (creatinine) 18) Known paraneoplastic syndrome or ectopic production of hormones by the primary tumor, which could lead to hypercalcemia, Cushing's syndrome, hypoglycemia, SIADH or carcinoid syndrome 19) Diabetes mellitus treated with insuline or corrected by oral hypoglycaemic agents if there is a history of clinically significant hypoglycaemia 20) Glaucoma 21) Untreated or imperfectly compensated hyperthyroidism 22) Any psychotic illness current or anamnestic from the range of diagnoses F2x.x 23) Current or anamnestic bipolar affective disorder F31.x and manic phase F30.x 24) Current severe depressive episode with psychotic symptoms F32.3 and F33.3 25) Presence of suicidal ideation / behavior based on clinical examination and / or Columbia-Suicide Severity Rating Scale (C-SSRS) of suicidal ideation / behavior based on C-SSRS version of Lifetime / Recent (L / R) (specifically answer "yes" to question 5 in the last 1 month and / or any “yes” answer to suicidal behavior questions in the last 3 months) 26) Organic mental disorders including symptomatic F00.x-F09.x 27) Psychotic disorders caused by the use of addictive substances (F10.x - F19.x), dissociative disorder (F44.x), eating disorders (F50.x), emotionally unstable, resp. border fault (F60.3) 28) Current or anamnestic alcohol or drug addiction F1x.x. (excluding opioids and medical cannabis used in accordance with controlled treatment of the underlying disease), unless abstinence can be demonstrated for at least 2 years 29) Undergoing electroconvulsive therapy less than 3 months ago 30) A relative of a first-order patient suffering from schizophrenia, another psychotic disorder (unless caused by a substance or medical condition) 31) Inadequacy of patient classification based on the clinical judgment of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of CT is to expand current therapeutic options for depression that accompanies cancer. The main potential benefit is a significant reduction in the mental suffering of these patients. It also compares the acute and long-term efficacy of two pharmacological experimental strategies of antidepressant response (psilocybin, ketamine).;Secondary Objective: 1. evaluation of the safety and tolerability of psilocybin in patients with comorbid depression • monitoring of adverse events throughout the study • somatic safety parameters: by monitoring the change in vital signs (blood pressure [BP], heart rate [BP]) during Sitting with the substance • mental safety parameters: by evaluating the BPRS and C-SSRS, SLV scores at the end of the Session, evaluating the persistent psychotropic effects of psilocybin using the PSQ scale 1 day after study medication administration 2. evaluation of the onset and duration of the antidepressant effect of psilocybin and ketamine • using the objective MADRS scale and the BECK self-assessment scale as a change in score Day 1, Day 4, 1 week (Day 7), 4 weeks (Day 28), 8 weeks (Day 56), 16 weeks (Day 112) ) and 24 weeks (day 224) from baseline study medication administration. ;Primary end point(s): 1. evaluation of the efficacy of psilocybin (active substance 1) in the treatment of depression comorbid to cancer 4 weeks (day 28) after its administration, by comparison with antidepressant ketamine (active substance 2) and midazolam (control substance) • parameter: evaluation using the total MADRS score between the baseline and the 28th day • in the case of a proven antidepressant response, the patient responder will be monitored for 24 weeks from the administration of the study medication in a double-blind follow-up section • In case of insufficient or absent antidepressant response, non-responders will be offered to continue the open extension of the study with the active substance. After unblinding of the study medicatio | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Evaluation of the onset of the antidepressant effect of psilocybin and ketamine (compared to midazolam) during the sitting with the substance • Parameter: change of BECK score on day 0 at the beginning of the day compared to BECK score on day 0 at the end of the day 2. Evaluation of the effect of psilocybin and ketamine (compared to midazolam) on quality of life and well-being • Parameter: change of FACIT score on day 7, 28, 224 compared to baseline 3. Evaluation of the effect of psilocybin and ketamine (compared to midazolam) on non-specific anxiety • Parameter: change of score on objective scale HAM-A and self-assessment scale STAI on day 1, 4, 7, 28, 56, 112, 224 compared to baseline 4. evaluation of the effect of psilocybin and ketamine (compared to midazolam) on the shift in life values • Parameter: evaluation using the PEQ scale on day 28, 224 against baseline 5. Evaluation of the effect of psilocybin and ketamine (compared to midazolam) on existential distress • Parameter: evaluation using the LAP-R scale on day 7, 28, 224 against baseline 6. Evaluation of the effect of psilocybin and ketamine (compared to midazolam) on subjectively perceived hopelessness • Parameter: evaluation using the HAI scale on day 7, 28, 224 against baseline 7. evaluation of the effect of psilocybin and ketamine (compared to midazolam) on demoralization • Parameter: evaluation using the DS scale on day 7, 28, 224 against baseline 8. Evaluation of the effect of psilocybin and ketamine (compared to midazolam) on the patient's subjective perception of pain • Parameter: evaluation using the VAS pain scale on day 7, 28, 224 versus baseline 9. evaluation of potential mediators of clinical response • Parameter: evaluation of acute psychological effects using subjective scales of 5D-ASCs and MEQ at the end of the day after the session with the substance 10. Comparison of the antidepressant effect of psilocybin and ketamine depending on the use of standard antidepres | — |
Countries
Czech Republic
Contacts
Public ContactFarmakologický ústav
Masarykova Univerzita
Outcome results
None listed