Lysergic Acid Diethylamide (LSD) in Palliative Care

Phase 2RecruitingNCT05883540

University Hospital, Basel, Switzerland60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Enrollment

Conditions

Palliative Care Pain Anxiety

Eligibility

Sex: ALLMin age: 22 Years

Medical Language ↔ Plain English

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 \< 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 \< 45 kg * Suicidal ideation with active intent or plan to act on suicidal thoughts as assessed by the treating investigator.

Locations (3)

Spital Uster AG

Uster, Canton of Zurich, Switzerland

RECRUITING

University Hospital Basel

Basel, Switzerland

RECRUITING

University Hospital Zurich, Clinic for Radio-Oncology, Competence Centre Palliative Care

Zurich, Switzerland

RECRUITING

Outcomes

Primary Outcomes

Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo

State anxiety inventory (STAI-S) scores, 20 items

Time frame: baseline, 2 weeks after second intervention

Secondary Outcomes

Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo

State anxiety inventory (STAI-S) scores, 20 items

Time frame: baseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention

Changes in pain levels assessed by questionnaire compared with active placebo

numeric rating scale (NRS) scores ranging from 0 (no pain) to 10 (maximum imaginable pain)

Time frame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

Changes in opioid use (dosages of opioids unified according to equivalent dosages of oral morphine) compared with active placebo

Time frame: 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

Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12) scores

Time frame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebo

Demoralization Scale II (DS-II) scores

Time frame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

Changes in quality of life assessed with a single-item question compared with active placebo

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)

Time frame: baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second intervention

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

Time frame: post drug visit 1-3 compared with post drug visit 4-6

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

Emotional Condition Rating Scale (ECRS) scores, Hamilton depression (GRID-HAM-D17) and Hamilton anxiety rating scale (HAM-A) scores

Time frame: baseline, one day before second intervention and 2 and 9 weeks after second intervention

Changes in patient's behaviour and attitudes rated by community observers compared with active placebo

community observer rating: rating of the participant's behaviour and attitudes on 11 items by a contact person

Time frame: baseline, before second intervention and 2 weeks and 9 weeks after second intervention

Changes in caregiver burden assessed by questionnaire compared with active placebo

Zarit Burden Inventory (ZBI) scores completed by caregiver, total score

Time frame: baseline, before second intervention and 2 weeks and 9 weeks after second intervention

Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires

acute effects will be assessed using the Mystical experience Questionnaire (MEQ30) and visual analogue scales (VASs)

Time frame: 2,4,6, and 9 weeks after second intervention

Changes in burden of suffering assessed with the Pictorial Representation of Illness and Self-Measure (PRISM) compared with active placebo

Time frame: 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

Time frame: baseline, 2 days after each intervention, 2 weeks and 9 weeks after second intervention

Expectancy as a mediator for treatment effects assessed with questionnaire

modified version of the Credibility / Expectancy Questionnaire (CEQ)

Time frame: baseline

Assessment of adverse events (AE)

grading according to Common Terminology Criteria for Adverse Events CTCAE Version 5.0, safety measures

Time frame: during the whole study duration up to 9 weeks after second intervention

Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints)

adapted list of complaints (LC), safety measures

Time frame: before and 12 hours after drug administration

Changes in vital signs during drug sessions

monitoring blood pressure and heart rate with an automatic oscillometric device, safety measure

Time frame: before and up to 12 hours after drug administration

Changes in vital signs during drug sessions

monitoring body temperature using an ear thermometer, safety measure

Time frame: before and up to 12 hours after drug administration

Lysergic Acid Diethylamide (LSD) in Palliative Care

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts