Pilot Study of Psilocybin-Assisted Therapy for Demoralization in Patients Receiving Hospice Care

Study Overview
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Brief Summary
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The overall objective of this study is to develop and pilot test a novel regimen of psilocybin-assisted psychotherapy for demoralization in patients receiving hospice care. -The name of the study drug involved in this study is Psilocybin

Detailed Description
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The purpose of this research is to understand how psilocybin-assisted therapy may be adapted in the context of hospice care, in order to test its safety in people with terminal illness who experience demoralization, and to study how well it works to lessen symptoms of psychological and existential distress. This research study involves a combined drug and psychotherapeutic (talk therapy) intervention. The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits. The treatment regimen consists of a single administration of psilocybin with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions The name of the study drug involved in this study is Psilocybin. Psilocybin is a naturally occurring psychedelic drug produced by more than 200 species of mushrooms, which is manufactured for medical use to control potency and purity. Participants will be followed for up to 24 weeks (approximately 6 months) after the study treatment. It is expected that about 15 people will take part in this research study. This research study is a Feasibility Study, which mean it is the first time investigators are examining psilocybin-assisted therapy in the context of hospice care. Psilocybin is an Investigational drug, meaning that the study drug has not been approved by the U.S. Food and Drug Administration (FDA) as a treatment for any disease. However, the FDA has granted psilocybin the status of breakthrough therapy in the treatment of depression and the investigators have permission from the FDA to use this drug in this research study.

Official Title
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Pilot Study of Psilocybin-Assisted Therapy for Demoralization in Patients Receiving Hospice Care - PATH Study

Conditions
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Hospice, Psilocybin, Demoralization, Terminal Illness, Cancer-related Problem/Condition, Psychotherapy, Terminal Cancer, Cancer Terminal

Intervention / Treatment
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* Drug: Psilocybin
* Behavioral: Psychotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled in hospice care at home Age ≥ 21 years. Any terminal illness with respect of exclusion criteria Palliative Performance Scale (PPS) ≥ 50 % (see Appendix A) Moderate-to-severe demoralization as measured by Demoralization Scale-II ≥ 8 Significant other or other caregiver present at home the night of study drug administration No driving for 24 hours following study drug administration. English proficiency Ability to understand and the willingness to sign a written informed consent document. Psilocybin is very likely to have no genotoxic effects. One study that directly focused on the mutagenic potential of psilocybin did not found this type of toxicity. However, due to the lack of clinical and non-clinical studies on the effects of psilocybin on the developing human fetus, women and men of child-bearing potential and who are sexually active must agree to use an acceptable contraceptive method (hormonal or barrier method of birth control; abstinence) throughout their participation in the study. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of psilocybin administration. Exclusion Criteria: Current General Inpatient (GIP) hospice status Patients currently receiving chemotherapy Condition impairing oral intake or digestive absorption Presence of a delirium diagnosed by the CAM Significant suicide risk as defined by suicidal ideation with intend and a plan as endorsed on item 5 on the C-SSRS within the past month or at V0 Current or past history of schizophrenia, psychotic disorder, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder, as assessed by medical history Patients with first-degree relatives with schizophrenia or bipolar disorder History of allergic reactions attributed to compounds of similar chemical or biologic composition to psilocybin Other personal circumstances and behavior that would limit compliance with study requirements, or judged by the study psychiatrist and/or principal investigator to be incompatible with establishment of rapport or safe exposure to psilocybin Potential for adverse drug-drug interactions. Concomitant medications with significant potential to interact with study medications will be exclusionary if they cannot be tapered. These include the following: Serotoninergic antidepressants Centrally-acting serotonergic agents (e.g. MAO inhibitors) Antipsychotics (e.g. first and second generation) Mood stabilizers (e.g. lithium, valproic acid) Aldehyde dehydrogenase inhibitors (e.g. disulfiram) Significant inhibitors of UGT 1A0 or UGT 1A10 Any psychiatric medication will be tapered if possible in an appropriate fashion to avoid withdrawal effects. They will be discontinued long enough before the psilocybin Session to avoid the possibility of any drug-drug interaction (the interval will be at least five times the particular drug and active metabolites' half-life). End stage liver disease or cirrhosis as primary hospice diagnosis Patients who have elevated AST and ALT five times above the normal laboratory limit on their last available bloodwork and patients with symptoms suggestive of liver failure including confusion, asterixis or jaundice. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal condition or any other unstable condition that, in the opinion of the principal investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study. This may include but is not limited to clinical symptoms or recent history of significant tachyarrhythmias; severe angina or myocardial ischemia; poorly controlled congestive heart failure; poorly controlled hypertension; poorly controlled hypo- or hyperthyroidism; uncontrolled diabetes; severe renal or liver disfunction; acute respiratory failure; sepsis; history of cerebral aneurysms; glaucoma; increased intracranial pressure and any intracranial mass. Women who are pregnant, nursing, or planning a pregnancy.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PATH<br>The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits. -The treatment regimen consists of a single administration of psilocybin 25 mg orally combined with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions | Drug: Psilocybin<br>* Oral, single administration, dosage 25 mg orally<br>Behavioral: Psychotherapy<br>* The treatment regimen consists of a single administration of psilocybin orally combined with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants screened per month | This measurement will assess enrollment feasibility based on the screening log. | Through study completion, an average of 1 year | 
| Number of participants enrolled per month | This measurement will assess enrollment feasibility based on the screening log. | Through study completion, an average of 1 year | 
| Average time delay from screening to enrollment | This measurement will assess enrollment feasibility based on the screening log. | Through study completion, an average of 1 year | 
| Mean number of sessions completed by enrolled participants | This measurement will assess retention feasibility. | Through study completion, an average of 1 year | 
| Proportion of planned assessments that are completed; duration of assessment visits | This measurement will evaluate assessment feasibility. | Through study completion, an average of 1 year | 
| Duration of assessment visits | This measurement will evaluate assessment feasibility. | Through study completion, an average of 1 year | 
| Mean score of acceptability ratings on Reactions to Research Participation Questionnaire Revised (RRPQR) | This measurement will assess acceptability. | At Week 1 post dosing session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Outcomes: Adverse Events (AEs) and Serious Adverse Events (SAEs) as assessed by treating Investigator/PI (MD) | Longitudinal follow-up and analysis of the relationship with psilocybin-assisted therapy. | Through study completion, an average of 1 year | 
| Safety Outcomes: Suicidal Risk as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Assessment of suicidal ideations or plans. The measurement of suicidal ideation is based on five yes or no questions with accompanying descriptions arranged in order of increasing severity. If the patient answers yes to either questions 1 or 2, the intensity of ideation is assessed in five additional questions related to frequency, duration, controllability, deterrents, and reasons for the most severe suicidal ideation. Suicidal behavior is assessed by asking questions categorizing behaviors into actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. A significant suicide risk is defined by suicidal ideation with intend and a plan as endorsed on item 5 on the C-SSRS within the past month at V0 or since previous visit later during the study. | From enrollment up to 10 days after dosing session | 
| Safety Outcomes: Delirium as assessed by Confusion Assessment Method (CAM) | Confusion Assessment Method (CAM) screens for a diagnosis of delirium via an assessment of the presence, severity and fluctuation of 9 delirium features: acute onset, inattention, disorganized thinking, altered level of consciousness, disorientation, memory impairment, perceptual disturbances, psychomotor agitation or retardation, and altered sleep-wake cycle. | From enrollment up to 10 days post dosing session | 
| Change in Global Quality Life Score as assessed by Functional Assessment of Chronic Illness Therapy - Palliative Care 14 (FACIT-Pal 14) | Functional Assessment of Chronic Illness Therapy - Palliative Care 14 (FACIT-Pal 14) consists in 14 items, and subjects rate how they felt during the previous week on a 5-point Likert scale | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 
| Change in Physical domain score as assessed by PROMIS Pain Interference Scale (PIS) | The PROMIS-Pain Interference Scale (PIS) measures the self-reported consequences of pain on relevant aspects of a person's life and may include the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. We will use 8 validated items pertaining to social and emotional consequences of pain during the previous week, that subjects will rate on a 5-point Likert scale | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 
| Change in Hospital Anxiety and Depression Scale (HADS A and D) Score | It is a self-report questionnaire consisting of 14 items, and subjects rate how they felt during the previous week on a 4-point Likert scale. The HADS consists of an anxiety and depression subscale (0-21 points each), and total scores can range from 0 to 42. Higher scores indicate more severe depression and anxiety. | At Baseline and every visit pre and post intervention (dosing session) up to 24 weeks | 
| Change in Life Attitude Profile - revised, Death acceptance subscale (LAP-R) Score | Life Attitude Profile - revised, Death acceptance subscale (LAP-R Death Acceptance) is a validated, self-rated 9-item, 7-point Likert scale assessing acceptance and anxiety about death | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 
| Change in Challenging Experience Questionnaire (CEQ) Score | The CEQ is a validated instrument with 26 items rated on a 5-item Likert scale, characterizing psychologically difficult aspects of experiences occasioned by psilocybin, according to seven factors: grief, fear, death, insanity, isolation, physical distress, and paranoia. | Immediately after the intervention, at the end of the dosing day | 
| Change in Social Isolation Scale (SIS) Score | The PROMIS SIS-6 assesses perceptions of being avoided, excluded, detached, disconnected from, or unknown by, others. We will use the short form of the instrument consisting in a 6-item, 5-point Likert scale | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 
| Change in Spiritual Domain Score as assessed by Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-sp-12) | The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-sp-12) scale is a measure of spiritual well-being validated for use in cancer and widely used in palliative care research. The FACIT-sp-12 has subscales that measure faith, meaning and peace, which are broadly consistent with conceptual models of spiritual wellbeing. | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 
| Change in Spiritual Domain Score as assessed by Schedule of Attitudes toward Hastened Death (SAHD) | The Schedule of Attitudes toward Hastened Death (SAHD) is a reliable and valid measure of desire for death among terminally ill patients. It includes 20 items that subjects rate as true or false. | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 
| Change in Spiritual Domain Score-Demoralization Scale (DS-II) | It's a 3-point response, self-report scale comprising 16 items and 2 subscales (meaning and purpose, and distress and coping ability). The presence of baseline moderate-to-severe demoralization, as measure by a DS-II score ≥ 8, is necessary for inclusion in this study. | At Baseline and every visit pre and post intervention (dosing session) up to 24 weeks | 
| Change in Spiritual Domain Score Mystical Experience Questionnaire (MEQ-30) | The MEQ-3056 is a self-report questionnaire that evaluates discrete mystical experiences induced by serotoninergic psychedelics and is sensitive to detecting psilocybin-induced mystical experiences. | Immediately after the intervention, at the end of the dosing day | 
| Change in Caregiver- CarGOQoL Score | The CarGOQoL is a well-designed and well-validated 29-item, multidimensional, self-administered questionnaire assessing QoL of cancer caregivers. | At Baseline, and every visit post intervention (dosing sessions) from Week 1 to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hospice, Psilocybin, Demoralization, Terminal Illness, Cancer related terminal illness, psychotherapy, Terminal Cancer, Cancer Terminal