CAPSI - Cancer related major depression treated with a single dose of psilocybin - a multicenter randomized placebo controlled double blind clinical trial

Phase 1

Conditions: Malignant tumours ICD 10 C00 to C97, Major Depressive Disorder
Therapeutic area: Diseases [C] - Neoplasms [C04]
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Registration Number: CTIS2023-505532-35-00

Lead Sponsor: Region Stockholm – SLSO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

1. signed informed consent via minavårdkontakter.se 2. Are 20 to 80 (inclusive) years old at the time of signed informed consent 3. Are able to read, speak, and understand Swedish 4. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations 5. Are able to swallow capsules 6. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of exposure to the Investigational Product, from Screening through the Day 8. 7. A diagnosis of a malignant neoplasm with a diagnostic code from C00 to C97 according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) 8. =1 month after cancer diagnosis and = 12 months of life expectancy at time of inclusion 9. physical functioning performance status 0-2 (WHO/ECOG) 10. Meet ICD-10 criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of a. at least a 30-day duration at the time of the Screening b. less than 1 year at time of Screening 11. Have moderate-severe depression symptoms at Screening, as defined by a Screening PHQ-9 total score = 10. 12. Are willing to abstain from other psychotherapeutic or antidepressant treatments during the study period (180 days; wash out time 5 half-lives). Note, if antidepressant treatment becomes needed as determined by the study physician this will be supported by the study personnel. 13. Have an identified support person. 14. Agree to be driven/accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing 49

Exclusion Criteria

1. Last contact with health care due to cancer monitoring or treatment >1 year ago. 2. Women who are pregnant, as indicated by a positive urine pregnancy test at Screening or Baseline. Women who intend to become pregnant during the study or who are currently nursing. 3. Unwilling or unable to discontinue formal psychotherapy 4. Ongoing antidepressant drug treatment. No interruption of ongoing antidepressant treatment will be done on the initiation of the study personnel. Patients will be encouraged to discuss any interruption with their responsible clinical physician. 5. Have previously during the current episode received the following non-medication treatments: a. deep brain stimulation (DBS) b. vagus nerve stimulation (VNS) 6. Currently receiving electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) 7. Unable or unwilling to discontinue any current medications that are known uridine diphosphate (UDP) or glucuronosyltransferase (UGT) enzyme modulators (eg valproate) Note: Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug plus one week at the time of Baseline. See Appendix A for a full list of prohibited medications. 8. Report psychedelic substances use ever o Note: Psychedelic substances include psilocybin, Lysergic acid diethylamide (LSD), mescaline (and natural products containing mescaline including peyote and San Pedro cactus), N,N-Dimethyltryptamine (DMT), natural products containing DMT including ayahuasca and 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 2C compounds, 3,4-methylenedioxy- methamphetamine (MDMA), methylone or other psychedelics. 9. Cancer at time of inclusion involving the CNS (as determined by a clinical examination or MRI) 10. Cancer treatment/follow up regime determined to be incompatible with the CAPSI protocol (eg due to time lines, interaction between cancer treatment and psilocybin 25 mg or 1 mg exposure). 11. Have any of the following cardiovascular conditions: a. congenital long QT syndrome (prior diagnosis), b. any of the following if disabling physical exercise similar to walking two stairs without pause: coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure, c. a clinically significant Screening ECG abnormality (e.g., atrial fibrillation); oNote: A QTcF interval > 450 milliseconds is considered a clinically significant ECG abnormality d. artificial heart valve; or 50 CAPSI protocol version no 1 date 230712 e. any other significant current or history of cardiovascular condition, based on the clinical judgment of study physician, that would make a participant unsuitable for the study 12. At Screening or Baseline have elevated blood pressure as defined as: a. Screening blood pressure SBP >150 mmHg or DBP > 95 mmHg on three separate readings; or b. Baseline blood pressure SBP >160 mmHg or DBP > 100 mmHg on three separate readings 13. Have a history of stroke or Transient Ischemic Attack (TIA) 14. Have moderate to severe hepatic impairment, as indexed by a Child-Pugh score = 7 15. Have uncontrolled epilepsy 16. Have insulin-dependent diabetes o Note: Participants who are taking oral hypoglycemic agent and have a history of hypoglycemia requiring medical intervention will be excluded 17. Are unable or unwilling to adhere to the following medication requirements: a. Agree to suspend sildenafil (Viagra®), tadalafil, or similar medications at least 72 hours prior to dosing 18. Have a positive