Lysergic Acid Diethylamide (LSD) in Palliative Care (LPC)

• ClinicalTrials.gov Identifier: NCT05883540
• Recruitment Status: Recruiting
• First Posted: June 1, 2023
• Last Update Posted: May 16, 2024
• Sponsor: University Hospital, Basel, Switzerland
• Collaborator: University Hospital, Zürich
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Palliative Care; Pain; Anxiety; Depression; Demoralization; Psychological Distress; Quality of Life; Caregiver Burden; Fear of Death; Existential Distress	Drug: Lysergic Acid Diethylamide Tartrate	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Lysergic Acid Diethylamide (LSD) in Palliative Care: a Randomised, Double-blind, Active-placebo Controlled Phase II Study (LPC-Study)
• Estimated Study Start Date: May 2024
• Estimated Primary Completion Date: September 2027
• Estimated Study Completion Date: September 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: treatment arm; Subjects in the treatment arm will receive 100 μg LSD (first session) and 100 or 200 μg LSD (second session) per os.	Drug: Lysergic Acid Diethylamide Tartrate; 100 or 200 μg p.o.; Other Name: LSD
Active Comparator: control arm; Subjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os.	Drug: Lysergic Acid Diethylamide Tartrate; 25 μg p.o.; Other Name: LSD

Outcome Measures

Primary Outcome Measures :

1. Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo [ Time Frame: baseline, 2 weeks after second intervention ]
   State anxiety inventory (STAI-S) scores, 20 items

Secondary Outcome Measures :

1. Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo [ Time Frame: baseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention ]
   State anxiety inventory (STAI-S) scores, 20 items
2. Changes in pain levels assessed by questionnaire compared with active placebo [ Time Frame: 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)
3. 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 ]
4. 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 [ Time Frame: 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
5. Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebo [ Time Frame: 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
6. Changes in quality of life assessed with a single-item question compared with active placebo [ Time Frame: 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)
7. Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second intervention [ Time Frame: 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
8. 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 [ Time Frame: 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
9. Changes in patient's behaviour and attitudes rated by community observers compared with active placebo [ Time Frame: 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
10. Changes in caregiver burden assessed by questionnaire compared with active placebo [ Time Frame: baseline, before second intervention and 2 weeks and 9 weeks after second intervention ]
    Zarit Burden Inventory (ZBI) scores completed by caregiver, total score
11. Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires [ Time Frame: 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)
12. 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 ]
13. 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 ]
14. Expectancy as a mediator for treatment effects assessed with questionnaire [ Time Frame: baseline ]
    modified version of the Credibility / Expectancy Questionnaire (CEQ)
15. Assessment of adverse events (AE) [ Time Frame: 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
16. Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints) [ Time Frame: before and 12 hours after drug administration ]
    adapted list of complaints (LC), safety measures
17. Changes in vital signs during drug sessions [ Time Frame: before and up to 12 hours after drug administration ]
    monitoring blood pressure and heart rate with an automatic oscillometric device, safety measure
18. Changes in vital signs during drug sessions [ Time Frame: before and up to 12 hours after drug administration ]
    monitoring body temperature using an ear thermometer, safety measure

Eligibility Criteria

• Ages Eligible for Study: 25 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 25 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, epilepsy with a history of 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
• concomitant diagnosis of past or present bipolar disorder
• 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.

Contacts and Locations

Contacts

Contact: Yasmin Schmid, MD; +41613286847; yasmin.schmid@usb.ch

Locations

Switzerland

University Hospital Basel; Recruiting

Basel, Switzerland

Contact: Yasmin Schmid, MD +41613286847 yasmin.schmid@usb.ch

Contact: Aaron Klaiber, MSc +41613284567 aaron.klaiber@usb.ch

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

Zürich, Switzerland

Contact: David Blum, Prof +41442553742 david.blum@usz.ch

Sponsors and Collaborators

University Hospital, Basel, Switzerland

University Hospital, Zürich

Investigators

• Principal Investigator: Yasmin Schmid, MD; University Hospital, Basel, Switzerland
• Principal Investigator: David Blum, Prof; University of Zurich

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT05883540
• Other Study ID Numbers: BASEC 2022-01818
• First Posted: June 1, 2023
• Last Update Posted: May 16, 2024
• Last Verified: May 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Caregiver Burden; Behavioral Symptoms; Stress, Psychological; Lysergic Acid Diethylamide; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Receptor Agonists