Anxiety, Caregiver Burden, Demoralization, Depression, Existential Distress, Fear of Death, Pain, Palliative Care, Psychological Distress, Quality of Life
Conditions
Brief summary
Background: Terminally ill patients often experience significant psychosocial distress having depressed mood, death anxiety, pain, and an overall poor quality of life. Recent evidence from pilot studies suggests that serotonergic hallucinogens including lysergic acid diethylamide (LSD) and psilocybin produce significant and sustained reductions of depressive symptoms and anxiety, along with increases in quality of life, and life meaning in patients suffering from life-threatening diseases. Additionally, serotonergic hallucinogens may produce antinociceptive effects. Objective and Design: The study aims to evaluate effects of LSD on psychosocial distress in 60 patients suffering from an advanced or end-stage fatal disease with a life expectancy ≥12wks and ≤2yrs in an active placebo-controlled double-blind parallel study. Patients will be allocated in a 2:1 ratio to one of the two intervention arms receiving either two moderate to high doses of LSD (100 µg and 100 µg or 100 µg and 200 µg) as intervention and two low doses of LSD (25 µg and 25 µg) as active-placebo control.
Interventions
25 μg p.o.
Sponsors
University Hospital, Basel, Switzerland
University Hospital, Zürich
Spital Uster AG, Uster, Switzerland
University Hospital, Geneva
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 22 years. * Advanced or End-stage fatal disease of any cause with a life expectancy ≥ 12 weeks and ≤ 2 years * Sufficient understanding of the study procedures and risks associated with the study. * Participants must be willing to adhere to the study procedures and sign the consent form. * Participants must be willing not to drive a traffic vehicle or to operate machines within 24 h after LSD administration. * Participants must complete an actual "Emergency Medical Directive" * Participants with central nervous system (CNS) involvement of cancer are eligible if the following apply: * treated and stable CNS lesion(s) OR untreated but asymptomatic/stable lesions, defined as clinically and/or radiologically stable for ≥ 4 weeks before screening * no seizures within ≥ 4 weeks; if on antiepileptic medication: stable dose ≥ 4 weeks and no relevant drug-drug interactions expected * no requirement for high-dose corticosteroids, defined as ≤10 mg prednisone equivalent per day on a stable or decreasing dose * no leptomeningeal metastases * no concomitant therapeutic anticoagulation
Exclusion criteria
* Life expectancy \< 12 weeks * Known hypersensitivity to LSD * Requiring ongoing concomitant therapy with a psychoactive prescription drug which might interfere with the study drug, and unable or unwilling to comply with the washout period. * Current use of a potent drug CYP2D6 inhibitor * Women who are pregnant or nursing or intend to become pregnant during the course of the study. * Somatic disorders including CNS involvement of cancer, untreated epilepsy with a history of generalized grand-mal seizures, history of delirium, end-stage heart failure (NYHA IV), untreated hypertension or insufficiently treated hypertension, angina pectoris, severe liver disease or severely impaired renal function, or other that in the judgement of the investigators pose too great potential for side effects. * Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant. * Participation in another study with an investigational drug within the 30 days preceding and during the present study * concomitant diagnosis of past or present psychotic disorder, first-degree relative with psychotic disorders * concomitant diagnosis of past or present bipolar disorder * current delirium * substance use disorder (within the last 2 months, except nicotine, opioids used for analgesia, and benzodiazepine treatment for anxiety). * Weight \< 45 kg * Suicidal ideation with active intent or plan to act on suicidal thoughts as assessed by the treating investigator. * CNS involvement of cancer if * CNS disease is unstable or high-risk, including clinically and/or radiologically progressive lesions, signs of raised intracranial pressure, radiologically uncontrolled edema, need for escalating corticosteroid doses, or any neurological condition judged to pose too excessive risk. * CNS-directed therapy (surgery and/or radiation) within ≤ 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo | baseline, 2 weeks after second intervention | State anxiety inventory (STAI-S) scores, 20 items |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo | baseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention | State anxiety inventory (STAI-S) scores, 20 items |
| Changes in pain levels assessed by questionnaire compared with active placebo | baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention | numeric rating scale (NRS) scores ranging from 0 (no pain) to 10 (maximum imaginable pain) |
| Changes in opioid use (dosages of opioids unified according to equivalent dosages of oral morphine) compared with active placebo | concomitant medication will be assessed several times over whole study duration up to 9 weeks after second intervention | — |
| Changes in spiritual well-being assessed by questionnaires (Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12)) compared with active placebo | baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention | Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12) scores |
| Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebo | baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention | Demoralization Scale II (DS-II) scores |
| Changes in quality of life assessed with a single-item question compared with active placebo | baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention | single-item question "how satisfied are you currently with your physical and emotional well-being" rated on a 7-point scale (1 dissatisfied, 7 satisfied) |
| Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second intervention | post drug visit 1-3 compared with post drug visit 4-6 | State anxiety inventory (STAI-S), NRS, QoL single-item, Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12), and Demoralization Scale II (DS-II) scores |
| Changes in patient's depression, isolation, anxiety, fear and denial of imminence of death, and pre-occupation with pain using investigator-ratings compared with active placebo | baseline, one day before second intervention and 2 and 9 weeks after second intervention | Emotional Condition Rating Scale (ECRS) scores, Hamilton depression (GRID-HAM-D17) and Hamilton anxiety rating scale (HAM-A) scores |
| Changes in patient's behaviour and attitudes rated by community observers compared with active placebo | baseline, before second intervention and 2 weeks and 9 weeks after second intervention | community observer rating: rating of the participant's behaviour and attitudes on 11 items by a contact person |
| Changes in caregiver burden assessed by questionnaire compared with active placebo | baseline, before second intervention and 2 weeks and 9 weeks after second intervention | Zarit Burden Inventory (ZBI) scores completed by caregiver, total score |
| Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires | 2,4,6, and 9 weeks after second intervention | acute effects will be assessed using the Mystical experience Questionnaire (MEQ30) and visual analogue scales (VASs) |
| Changes in burden of suffering assessed with the Pictorial Representation of Illness and Self-Measure (PRISM) compared with active placebo | baseline, 2 days after each intervention, 2 weeks and 9 weeks after the second intervention | — |
| Qualitative description of subjective changes after intervention assessed with semistructured interviews | baseline, 2 days after each intervention, 2 weeks and 9 weeks after second intervention | — |
| Expectancy as a mediator for treatment effects assessed with questionnaire | baseline | modified version of the Credibility / Expectancy Questionnaire (CEQ) |
| Assessment of adverse events (AE) | during the whole study duration up to 9 weeks after second intervention | grading according to Common Terminology Criteria for Adverse Events CTCAE Version 5.0, safety measures |
| Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints) | before and 12 hours after drug administration | adapted list of complaints (LC), safety measures |
| Changes in vital signs during drug sessions | before and up to 12 hours after drug administration | monitoring blood pressure and heart rate with an automatic oscillometric device, safety measure |
Countries
Switzerland
Contacts
CONTACTYasmin Schmid, PD Dr. med.
PRINCIPAL_INVESTIGATORYasmin Schmid, PD Dr. med.
University Hospital, Basel, Switzerland
Outcome results
None listed