PsyPal; Psilocybin Therapy for Psychological Distress in Palliative Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Nervous System Diseases [C10], Phenomena and Processes [G] - Biological Phenomena [G16], Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Psychiatry and Psychology [F] - Psychological Phenomena [F02], Psychiatry and Psychology [F] - Mental Disorders [F03], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

1 Jun 2025 → ongoing

Decision date (initial)

2024-11-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

EU Horizon Grant

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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).

Secondary objectives 7

1. To determine the response rate to psilocybin therapy, defined as a ≥50% reduction in MADRS score between baseline and primary endpoint
2. To evaluate the effect of psilocybin therapy on end-of-life anxiety, as measured by the change in DADDS score between baseline and primary endpoint.
3. To evaluate the effect of psilocybin therapy on symptoms of anxiety and depression, as measured by the change in HADS score between baseline and primary endpoint.
4. To assess the impact of psilocybin therapy on demoralization, as measured by the change in Demoralisation Scale-II (DS-II) between baseline and primary endpoint.
5. To evaluate the effect of psilocybin therapy on health-related quality of life, as measured by the change in EQ-5D-5L between baseline and primary endpoint.
6. To assess the impact of psilocybin therapy on caregiver burden, as measured by the change in Zarit Burden Interview (ZBI-7) between baseline and primary endpoint.
7. To assess the impact of psilocybin therapy on clinical functioning, as measured by the change in disease-specific measures between baseline and primary endpoint: a. COPD  COPD Assessment Test (CAT)  St George's respiratory questionnaire (SGRQ-C)  Lung function (FEV1, RV, TLC, and IRC) o ALS  Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R)  Amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-5) o MS  Expanded Disability Status Scale (EDSS)  McDonald criteria o APD  Parkinson's Disease Questionnaire (PDQ-8)  Unified Parkinson's Disease Rating Scale (MDS-UPDRS)  Rey Auditory Verbal Learning Test (RAVLT)  Letters and Numbers Sequence  Trail Making Test (TMT)  Verbal Fluency  Digit Span  Digit Symbol Substitution Test  Irregular Word Reading Test (TeLPI)

Conditions and MedDRA coding

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).

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. COPD: diagnosis by specialist
2. COPD: Postbronchodilator FEV1/FVC < 0,7 and FEV1 <80% pred
3. COPD: ≥ 40 years old
4. COPD: ≥ 10 years smoking
5. ALS: ALS according to Goldcoast criteria
6. 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
7. MS: Fulfilled diagnostic revised McDonald criteria for MS from 2017
8. MS: EDSS ≥ 1,0
9. 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
10. APD: Diseases in the spectrum of Progressive supranuclear palsy (PSP), fulfilling possible and probable criteria, according to the MDS diagnostic criteria
11. APD: Clinically Established and Clinically Probable Multiple System Atrophy (MSA) according to the MDS diagnostic criteria
12. 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
13. Patient has a MADRS score of > 19
14. Patient should have a life expectancy of at least 6 months (assessed by study physician)
15. Patient is at least 18 years of age
16. Patient has an identified caregiver/support person
17. 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
18. 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
19. Patient is able to ingest capsules

Exclusion criteria 23

1. Patient has used a psychedelic substance in the past 6 months (e.g., psilocybin, LSD, 5-MeO-DMT, DMT, ayahuasca or mescaline)
2. Patient is in active treatments for other psychiatric disorders, judged by the screening clinician to be a more significant clinical problem than depression / distress
3. 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
4. Patients with any lifetime diagnosis of schizophrenia spectrum or other psychotic disorders
5. 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).
6. Patients with a pre-existing psychiatric condition judged to be incompatible with safe exposure to psilocybin therapy
7. 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
8. Patient meets ICD-10 criteria for active/current alcohol or drug use disorder
9. 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)
10. Patient is unwilling or unable to pause formal psychotherapy (days 0-42)
11. 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
12. 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).
13. Patient has moderate to severe hepatic impairment (Child-Pugh score ≥ 7)
14. Patient has insulin-dependent diabetes or who are taking oral hypoglycaemic agents and have a current risk of hypoglycaemia that would require medical intervention
15. 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
16. Patient has an allergy or intolerance to any of the materials contained in either drug product
17. 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
18. Recent (2 weeks) change or planned change in antidepressant medication during the intervention
19. 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).
20. COPD: Unresolved exacerbation or pulmonary infection within last 4 weeks
21. ALS: Significant cognitive deficits (MoCA)
22. MS: Significant cognitive deficits (MoCA), epilepsy or radiologically isolated syndrome
23. APD: Dementia (MoCa), or Schwab and England ADL scale with scores > 80% in the best functional state

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 1

1. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Prof. Dr. Robert Schoevers

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Prof. Dr. Robert Schoevers

Third parties 3

Locations

4 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications