Psilocybin Therapy for Psychological Distress in Palliative Patients

NCT06782724 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 188702023-510488-36-01
• Study Type: interventional
• Target: 108
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate whether psilocybin therapy can effectively treat depression and psychological distress in adult patients with COPD, ALS, MS, or APD who have at least 6 months life expectancy. The main questions it aims to answer are:

• Can psilocybin therapy safely reduce depressive symptoms compared to low-dose control?
• Will the therapeutic effects be rapid and sustained over a 6-month period? Researchers will compare patients receiving two escalating doses of psilocybin (15mg followed by 25mg) against those receiving two low doses (1mg) to see if the higher doses lead to greater improvements in depression, anxiety, demoralization, and quality of life. Participants will:
• Attend three preparation sessions with psychotherapists (1-2 hours each)
• Undergo two supervised psilocybin dosing sessions (6-8 hours each)
• Complete five integration therapy sessions following the dosing sessions
• Participate in follow-up assessments at 6 weeks, 3 months, and 6 months
• Have access to a digital care platform and peer support groups during the 6-month follow-up period
• Optional: Control group participants may receive one high-dose psilocybin session (25mg) after the initial study period

Conditions

COPD (Chronic Obstructive Pulmonary Disease); ALS (Amyotrophic Lateral Sclerosis); MS (Multiple Sclerosis); Major Depressive Disorder (MDD); Atypical Parkinson Disease

Keywords

psilocybin; therapy; palliative; care; palliative care; end-of-life distress; depression; psychological distress; psypal; copd; als; ms; apd; chronic obstructive pulmonary disorder; amyotrophic lateral sclerosis; multiple sclerosis; major depressive disorder; atypical parkinson disease; existential distress

Outcome Measures

Primary Outcomes (1)

• Depressive symptoms (MADRS)

  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.

  Baseline (Day -14) to Primary Endpoint (Day 56)

Secondary Outcomes (15)

• Response rate

  Baseline (Day -14) to Primary Endpoint (Day 56)

• End-of-life anxiety

  Baseline (Day -14) to Primary Endpoint (Day 56)

• Anxiety and depression (symptoms)

  Baseline (Day -14) to Primary Endpoint (Day 56)

• Demoralization

  Baseline (Day -14) to Primary Endpoint (Day 56)

• Impact on Quality of life

  Baseline (Day -14) to Primary Endpoint (Day 56)

Other Outcomes (28)

• Experiential avoidance

  Baseline to Primary Endpoint (Day 56)

• Coping

  Baseline to Primary Endpoint (Day 56)

• The wish to hasten death

  Baseline to Primary Endpoint (Day 56)

Study Arms (2)

Moderate (15mg) and high dose (25mg) psilocybin group

EXPERIMENTAL

Patients assigned to this arm will first receive three prepration sessions followed by one moderate dose (15mg) of psilocybin. Patients will then receive two integration sessions and a high dose (25mg) of psilocybin. This is followed by three integration sessions.

Drug: Psilocybin therapy

Low-dose (1mg) psilocybin group

PLACEBO COMPARATOR

Patients assigned to this arm will first receive three prepration sessions followed by one low dose (1mg) of psilocybin. Patients will then receive two integration sessions and another low dose (1mg) of psilocybin. This is followed by three integration sessions.

Drug: Psilocybin therapy

Interventions

Psilocybin therapy DRUG

Psilocybin therapy consisting of three preparation, two dosing, and three integration sessions. All sessions will take place in a controlled, safety environment and supported by two study therapists

Low-dose (1mg) psilocybin group; Moderate (15mg) and high dose (25mg) psilocybin group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has to be diagnosed with one of the following four conditions, defined as:
• COPD i) Diagnosis by medical specialist ii) Postbronchodilator FEV1/FVC \< 0,7 and FEV1 \<80% pred iii) ≥ 40 years old iv) ≥ 10 years smoking
• ALS i) ALS according to Goldcoast criteria (Shefner et al, Clin Neurophysiol, 2020) ii) 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 i) Fulfilled diagnostic revised McDonald criteria for MS from 2017 (Thompson et al., 2018) ii) EDSS ≥ 1,0
• APD i) 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 ii) Diseases in the spectrum of Progressive supranuclear palsy (PSP), fulfilling possible and probable criteria, according to the MDS diagnostic criteria iii) 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 com-pletion of the mood section of the Mini International Neuropsychiatric Interview by a screen-ing 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. See specific conditions for Czechia in Appendix 5.
• 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.

You may not qualify if:

• Patient has used a psychedelic substance in the past 6 months (e.g., psilocybin, LSD, 5-MeO-DMT, DMT, ayahuasca or mescaline).
• Patient is in active treatments for other psychiatric disorders, judged by the screening clinician to be a more significant clinical problem than depression / distress.
• 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 for Prohibited medications).
• 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.
• COPD: Unresolved exacerbation or pulmonary infection within last 4 weeks. ALS: Significant cognitive deficits (MoCa, see below). MS: Significant cognitive deficits (MoCa, see below), epilepsy or radiologically isolated syndrome.
• APD: Dementia (MoCa, see below), or Schwab and England ADL scale with scores \> 80% in the best functional state.
• 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).

Sponsors & Collaborators

• University Medical Center Groningen: lead
• HumanKindLabs: collaborator
• University of Copenhagen: collaborator
• CTC Clinical Trial Consultants AB: collaborator
• OPEN Foundation: collaborator
• IESE Business School: collaborator
• Uppsala University: collaborator
• The Champalimaud Centre, Lisbon, Portugal: collaborator
• Stockholm University: collaborator
• University of Groningen, The Netherlands: collaborator
• National Institute of Mental Health, Czech Republic: collaborator
• European Association for Palliative Care (EAPC): collaborator
• Madopa: collaborator
• Bispebjerg Hospital: collaborator
• European Association of Neurological Associations (EFNA): collaborator
• 29k International AB: collaborator
• Lung Alliance Netherlands: collaborator
• European Psychiatric Association: collaborator
• Norrsken Mind: collaborator

Related Links

• Official website for PsyPal

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Amyotrophic Lateral Sclerosis; Multiple Sclerosis; Depressive Disorder, Major; Parkinson Disease, Familial, Type 1; Depression

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Central Study Contacts

Robert A Schoevers, Professor

CONTACT

050 361 2008; r.a.schoevers@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized double-blind low-dose controlled clinical trial

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 20, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share