PSILOCYBINE for Chronic obstructive pulmonary disease | Amyotrophic lateral sclerosis | Multiple sclerosis | Atypical Parkinsonism (including multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome)

Inclusion criteria

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

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

Primary endpoints

• {"endpoint_text":"- 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..","definition_or_measurement_approach":"Change in depressive symptoms measured using the clinician-administered Montgomery Åsberg Depression Rating Scale (MADRS), comparing scores at Baseline and at 6 weeks after Dose 2 between high/medium-dose psilocybin group and low-dose control."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured using multiple validated instruments: response rate (≥50% reduction in MADRS), DADDS for end-of-life anxiety, HADS for anxiety/depression, Demoralisation Scale-II (DS-II), EQ-5D-5L for quality of life, Zarit Burden Interview (ZBI-7) for caregiver burden, and disease-specific measures (e.g., CAT, SGRQ-C, lung function for COPD; ALSFRS-R and ALSAQ-5 for ALS; EDSS and McDonald criteria for MS; PDQ-8, MDS-UPDRS, RAVLT, TMT, Verbal Fluency, Digit Span, Digit Symbol Substitution Test, TeLPI for APD)."}

Netherlands

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

564

Number Of Sites

1

Number Of Participants

27

Czechia

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

552

Number Of Sites

1

Number Of Participants

27

Portugal

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

546

Number Of Sites

1

Number Of Participants

27

Denmark

Earliest CTIS Part Ii Submission Date

01-11-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

543

Number Of Sites

1

Number Of Participants

27

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Contract research organisations

Name

CTC Clinical Trial Consultants AB

Responsibilities

Arrange monitoring for Danish, Portoguese and Czech site

Third parties

• {"country":"Sweden","full_name":"CTC Clinical Trial Consultants AB","duties_or_roles":"sponsorDuties codes: 1, 15; Arrange monitoring for Danish, Portoguese and Czech site","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Groningen","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Avextra Pharma GmbH","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}