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)

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 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

• Drug Lysergic Acid Diethylamide Tartrate
  25 μg p.o.
• Drug Lysergic Acid Diethylamide Tartrate
  100 or 200 μg p.o.

Primary outcome measures

• Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo [Time frame: baseline, 2 weeks after second intervention]

Secondary outcome measures (12)

• 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]
• 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]
• 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 [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 [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 [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 [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 [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 [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 [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 [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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Supportive care

Study locations

Switzerland · 4 centers

• University Hospital Basel, Division of Clinical Pharmacology and Toxicology — Basel
• University Hospital Geneva, Palliative medicine department — Collonge-Bellerive
• Spital Uster AG, Division of Internal Medicine — Uster
• University Hospital Zurich, Clinic for Radio-Oncology, Competence Centre Palliative Care — Zurich

Publications

• Schipper S, Nigam K, Schmid Y, Piechotta V, Ljuslin M, Beaussant Y, Schwarzer G, Boehlke C. Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database Syst Rev. 2024 Sep 12;9(9):CD015383. doi: 10.1002/14651858.CD015383.pub2. PMID 39260823

Identifiers

NCT: NCT05883540 · BASEC 2022-01818

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗