Clinical trial NCT05883540: Lysergic Acid Diethylamide (LSD) in Palliative Care
Official title: Lysergic Acid Diethylamide (LSD) in Palliative Care: a Randomised, Double-blind, Active-placebo Controlled Phase II Study (LPC-Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Palliative Care
Pain
Anxiety
Depression
Demoralization
Psychological Distress
Quality of Life
Caregiver Burden
Fear of Death
Existential Distress
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University Hospital, Zürich
name: Spital Uster AG, Uster, Switzerland
First posted: 2023-06-01
Enrollment: 60
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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 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.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 22 years.
* 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"

Exclusion Criteria:

* Life expectancy \&lt; 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 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 \&lt; 45 kg
* Suicidal ideation with active intent or plan to act on suicidal thoughts as assessed by the treating investigator.

Primary outcomes:
measure: Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo
timeFrame: baseline, 2 weeks after second intervention
Secondary outcomes:
measure: Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo
timeFrame: baseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention
measure: Changes in pain levels assessed by questionnaire compared with active placebo
timeFrame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
measure: Changes in opioid use (dosages of opioids unified according to equivalent dosages of oral morphine) compared with active placebo
timeFrame: concomitant medication will be assessed several times over whole study duration up to 9 weeks after second intervention
measure: 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
timeFrame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
measure: Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebo
timeFrame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
measure: Changes in quality of life assessed with a single-item question compared with active placebo
timeFrame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
measure: Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second intervention
timeFrame: post drug visit 1-3 compared with post drug visit 4-6
measure: 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
timeFrame: baseline, one day before second intervention and 2 and 9 weeks after second intervention
measure: Changes in patient's behaviour and attitudes rated by community observers compared with active placebo
timeFrame: baseline, before second intervention and 2 weeks and 9 weeks after second intervention
measure: Changes in caregiver burden assessed by questionnaire compared with active placebo
timeFrame: baseline, before second intervention and 2 weeks and 9 weeks after second intervention
measure: Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires
timeFrame: 2,4,6, and 9 weeks after second intervention
measure: Changes in burden of suffering assessed with the Pictorial Representation of Illness and Self-Measure (PRISM) compared with active placebo
timeFrame: baseline, 2 days after each intervention, 2 weeks and 9 weeks after the second intervention
measure: Qualitative description of subjective changes after intervention assessed with semistructured interviews
timeFrame: baseline, 2 days after each intervention, 2 weeks and 9 weeks after second intervention
measure: Expectancy as a mediator for treatment effects assessed with questionnaire
timeFrame: baseline
measure: Assessment of adverse events (AE)
timeFrame: during the whole study duration up to 9 weeks after second intervention
measure: Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints)
timeFrame: before and 12 hours after drug administration
measure: Changes in vital signs during drug sessions
timeFrame: before and up to 12 hours after drug administration
measure: Changes in vital signs during drug sessions
timeFrame: before and up to 12 hours after drug administration
Other outcomes:
Locations:
city: Uster
country: Switzerland
facility: Spital Uster AG
state: Zurich
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Zürich
country: Switzerland
facility: University Hospital Zurich, Clinic for Radio-Oncology, Competence Centre Palliative Care
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Yasmin Schmid, MD
role: PRINCIPAL_INVESTIGATOR
References: