PsyPal; Psilocybin Therapy for Psychological Distress in Palliative Patients

Phase 2

Not yet recruiting

Conditions: Chronic obstructive pulmonary disease (COPD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and atypical Parkinson disorder (APD), particularly multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS).

Registration Number: 2023-510488-36-01

Lead Sponsor: Universitair Medisch Centrum Groningen

Brief Summary: To examine medium/high-dose psilocybin therapy safety and efficacy in reducing symptoms of depression in patients with COPD, ALS, MS, or APD, compared to the low-dose control group. This will be determined by using the clinician-administered Montgomery Åsberg Depression Rating Scale (MADRS) score and comparing changes between scores at Baseline and Primary endpoint (6 weeks post Dose 2).

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 108

Inclusion Criteria

COPD: diagnosis by specialist

APD: Diseases in the spectrum of Progressive supranuclear palsy (PSP), fulfilling possible and probable criteria, according to the MDS diagnostic criteria

APD: Clinically Established and Clinically Probable Multiple System Atrophy (MSA) according to the MDS diagnostic criteria

Patient meets ICD-10 criteria for major depressive disorder documented through the completion of the mood section of the Mini International Neuropsychiatric Interview by a screening psychologist or physician

Patient has a MADRS score of > 19

Patient should have a life expectancy of at least 6 months (assessed by study physician)

Patient is at least 18 years of age

Patient has an identified caregiver/support person

Patient is able to read and understand the informed consent and all scales used in a local language. For those with ALS, MS, or APD, competency is ensured via neurologist assessment, cognitive screening, caregiver support during screening and interactive approaches where the screening clinician ask the patient to explain their understanding of consent elements, re-explaining potentially misunderstood information

Patient is able to and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations

Patient is able to ingest capsules

COPD: Postbronchodilator FEV1/FVC < 0,7 and FEV1 <80% pred

COPD: ≥ 40 years old

COPD: ≥ 10 years smoking

ALS: ALS according to Goldcoast criteria

ALS: ALS-FRS-R subscores of minimum 1 in item 2, 3 and 8, subscore of minimum 2 in item 1, 4 and 10 and a subscore of minimum 3 in item 11 and 12

MS: Fulfilled diagnostic revised McDonald criteria for MS from 2017

MS: EDSS ≥ 1,0

APD: Advanced to Late-Stage Parkinson’s Disease – patients with a diagnosis of Parkinson’s Disease per the MDS clinical diagnosis criteria with evidence of motor and non-motor fluctuations

Exclusion Criteria

Patient has used a psychedelic substance in the past 6 months (e.g., psilocybin, LSD, 5-MeO-DMT, DMT, ayahuasca or mescaline)

Patient is unwilling or unable to pause formal psychotherapy (days 0-42)

Patient has neurological conditions (e.g., intracranial tumour, epilepsy, brain injuries, or other neurological disorders) expected by the PIs to conflict with the treatment / study protocol

Cardiovascular conditions: recent stroke (< 1 year from signing of ICF), recent myocardial infarction (< 1 year from signing of ICF), uncontrolled hypertension (blood pressure > 140/90 mmHg), clinically significant arrhythmia within 1 year of signing the ICF, or QTc prolongation exceeding 450ms (males) / 470ms (females).

Patient has moderate to severe hepatic impairment (Child-Pugh score ≥ 7)

Patient has insulin-dependent diabetes or who are taking oral hypoglycaemic agents and have a current risk of hypoglycaemia that would require medical intervention

Patient has any physical or psychological symptoms, medications, blood test results or clinically significant findings at Screening or Baseline (based on the clinical judgement of clinical/medical study personnel) that would make a patient unsuitable for the study

Patient has an allergy or intolerance to any of the materials contained in either drug product

Cognitive and Neuropsychological assessment: Patients will be excluded if they score below mean minus 1.5 Standard Deviation according to normative age and scholarity adjusted data on the Montreal Cognitive Assessment (MoCA) assessment

Recent (2 weeks) change or planned change in antidepressant medication during the intervention

Women who are pregnant, intend to become pregnant during the study, who are currently nursing or are unwilling to use Highly Effective Contraceptive Methods (section 8.2.1).

Patient is in active treatments for other psychiatric disorders, judged by the screening clinician to be a more significant clinical problem than depression / distress

COPD: Unresolved exacerbation or pulmonary infection within last 4 weeks

ALS: Significant cognitive deficits (MoCA)

MS: Significant cognitive deficits (MoCA), epilepsy or radiologically isolated syndrome

APD: Dementia (MoCa), or Schwab and England ADL scale with scores > 80% in the best functional state

Patient meets ICD-10 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features (except substance/medication-induced or due to another medical condition) or bipolar I/II disorder

Patients with any lifetime diagnosis of schizophrenia spectrum or other psychotic disorders

Patient has a first-degree relative with schizophrenia spectrum, bipolar I disorder or other psychotic disorders (expect substance/medication-induced or due to another medical condition).

Patients with a pre-existing psychiatric condition judged to be incompatible with safe exposure to psilocybin therapy

Significant suicide risk as defined by (1) suicidal ideation with intent to act (defined as ≥ 5 on MADRS item 10), (2) suicidal attempts within the past year, or (3) clinical assessment of significant suicidal risk during patient interview

Patient meets ICD-10 criteria for active/current alcohol or drug use disorder

Patient has ongoing treatment with antipsychotic drugs. Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug at the time of baseline (see Appendix 1a of the Clinical Trial Protocol for Prohibited medications)

Study & Design

Study Type: Not specified

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the change in depressive symptoms from baseline to 6 weeks after the second dose of psilocybin (high dose session) compared low-dose control..		The primary endpoint is the change in depressive symptoms from baseline to 6 weeks after the second dose of psilocybin (high dose session) compared low-dose control..

Secondary Outcome Measures

Name	Time	Method
To assess change in clinical functioning, end-of-life anxiety, psychological/existential distress, health-related quality of life, and how it impacts caregiver ’s health- and economic burden.		To assess change in clinical functioning, end-of-life anxiety, psychological/existential distress, health-related quality of life, and how it impacts caregiver ’s health- and economic burden.

Trial Locations

Locations (4): Narodni Ustav Dusevniho Zdravi
🇨🇿
Klecany, Czechia
Universitair Medisch Centrum Groningen
🇳🇱
Groningen, Netherlands
Champalimaud Clinical Centre
🇵🇹
Lisbon, Portugal
Region Hovedstaden
🇩🇰
Copenhagen Nv, Denmark
Narodni Ustav Dusevniho Zdravi
🇨🇿Klecany, Czechia
Tomas Palenicek
Site contact
+420261363387
Tomas.Palenicek@nudz.cz