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LSD Therapy for Persons Suffering From Major Depression (LAD)

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ClinicalTrials.gov Identifier: NCT03866252
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : February 9, 2021
Sponsor:
Collaborator:
Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE February 8, 2019
First Posted Date  ICMJE March 7, 2019
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE November 1, 2019
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
Change in depressive symptomatology assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD ]
Inventory of Depressive Symptomatology (IDS-SR, IDS-C, self-rated and clinician-rated). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 84 and higher scores indicating more and/or stronger depressive symptoms.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: March 4, 2019)
  • Change in depressive symptoms assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD ]
    Beck Depression Inventory (BDI). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 63 and higher scores indicating more and/or stronger depressive symptoms.
  • Changes in state and trait anxiety assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 2 weeks post-intervention ]
    State-Trait Anxiety Inventory (STAI). State and trait anxiety are being assessed separately. Each type of anxiety is being represented by 20 different items. Scores range from 20 to 80, with higher scores indicating greater anxiety.
  • Changes in general psychopathology assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD ]
    Symptom Check List (SCL-90, 90-item version). Consists of 9 subscales investigating psychopathological symptoms (somatization, obsessive-compulsivity, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism), offering five answers (i.e. not at all, a little, fairly, a lot, extremely). SCL-90 total score = 360; subscale total score = 40. Higher scores indicate greater psychological impairment.
  • Changes in existential anxiety assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment ]
    Existential Concerns Questionnaire (EAQ). Item scores are assessed in a yes/no format.
  • Changes in mindfulness assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment ]
    Five Facet Mindfulness Questionnaire (FFMQ). Item scores are assessed on a scale from 1 (never) to 5 (very often or always). Higher scores indicate higher greater levels of mindfulness.
  • Changes in humility assessed by questionnaire compared with active placebo [ Time Frame: Baseline; 6 weeks post-treatment ]
    Elliot Humility Scale (EHS). Item scores are assessed on a scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher greater levels of humility.
  • Changes in humility assessed by questionnaire [ Time Frame: Baseline; 6 weeks post-treatment compared with active placebo ]
    Jankowski Humility Scale (JHS). Item scores are assessed on a scale from 1 (not at all) to 5 (absolutely). Higher scores indicate higher greater levels of humility.
  • Changes in the personality trait "absorption" assessed by questionnaire compared with active placebo [ Time Frame: Baseline ]
    Tellegen Absorption Scale (TAS). Item scores are assessed on a scale from 0 (not at all) to 4 (absolutely). Higher scores indicate higher greater levels of trait absorption.
  • Acute subjective effects assessed via questionnaire compared with active placebo [ Time Frame: At weeks 3 and 7 ]
    The Visual Analog Scale (VAS). Items assess acute subjective drug effects (e.g. intensity, liking) Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects.
  • Characteristics of altered states of consciousness assessed by questionnaire [ Time Frame: At weeks 3 and 7 ]
    States of Consciousness Questionnaire (SCQ). Items retrospectively assess subjective drug effects. Item scores are assessed on a scale ranging from 0 to 5. Higher scores indicate greater subjective effects associated with a different state of consciousness.
  • Characteristics of altered states of consciousness assessed by questionnaire compared with active placebo [ Time Frame: At weeks 3 and 7 ]
    5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Items retrospectively assess subjective drug effects. Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects associated with a different state of consciousness.
  • Changes in mystical-type experiences assessed by questionnaire [ Time Frame: Baseline; 6 weeks post-treatment compared with active placebo ]
    Mysticism Scale (MS). Item scores are assessed on a scale ranging from +4 (extremely accurate) to -4 (extremely inappropriate). Higher scores indicate greater levels of mystical experiences.
  • Acquisition of physical conditions / complaints assessed by questionnaire [ Time Frame: Baseline; at weeks 2, 3, 5, 7, 9, 13 ]
    List of complaints (LC). Assesses acute complaints (e.g. pain, coughing, nausea) in a yes/no frmat. A higher number of "yes" answers indicates more complaints. Total "yes" score ranges from 0 to 65.
  • Perception of therapeutic alliance assessed by questionnaire [ Time Frame: 1 week pre-treatment ]
    Helping Alliance Questionnaire (therapist version (HAQ-T), patient version (HAQ-P). Item scores are assessed on a scale ranging from 1 (very accurate) to 6 (very inaccurate). Lower scores indicate increased subjective helping alliance.
  • Subjective evaluation of mood assessed by questionnaire [ Time Frame: Baseline; at weeks 2, 3, 5, 7, 9, 13 ]
    Adjective Mood Rating Scale (clinician version (AMRS-C), patient version (AMRS-P). Scale consists of 60 adjectives describing different moods (e.g. "nervous", "concentrated", "drowsy"), offering four response possibilities (i.e. not at all, a little, fairly, strongly). Items are analyzed separately.
  • Assessment of personality by questionnaire [ Time Frame: Baseline ]
    NEO-Five-Factor-Inventory (NEO-FFI). The NEO-FFI assesses five personality traits (i.e. neuroticism, extraversion, openness, agreeableness and conscientiousness) on a scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher manifestation of a particulare personality trait.
  • Assessment of religiosity by questionnaire [ Time Frame: Baseline ]
    Religiosity Scale (Z-Scale). This 7-item scale assesses the degree of religiosity on ascending scales ranging from "not at all" to "very often". Higher scores indicate higher levels of religiosity.
  • Persisting effects of treatment assessed by questionnaire [ Time Frame: 12 weeks post-treatment ]
    Persisting Effects Questionnaire (PEQ). Scores are assessed on a scale from 0 (not at all) to 5 (extremely). Higher scores (under consideration of reverse-scored items) indicate stronger persisting treatment effects.
  • Changes in brain-derived neurotrophic factor (BDNF) [ Time Frame: One day and 12 weeks post-treatment ]
    Changes in brain-derived neurotrophic factor as measured by blood concentrations compared with active placebo
  • Changes in hypothalamic-pituitary-adrenal (HPA) axis function [ Time Frame: 2 weeks post-treatment ]
    Changes in hypothalamic-pituitary-adrenal (HPA) axis function as measured with salivary cortisol awakening responses compared with active placebo
  • Changes in immunoregulation and Inflammation compared with active placebo [ Time Frame: One day and 12 weeks post-treatment ]
    Measured via blood levels of macrophage migration inhibitory factor and interleukin-1 beta
  • Brain activation during fearful face processing and working memory processing compared with placebo [ Time Frame: One week pre-treatment and one day post-treatment ]
    Functional Magnetic Resonance Imaging (fMRI)
  • Brain Perfusion in treatment condition compared with active placebo [ Time Frame: One week pre-treatment and one day post-treatment ]
    Diffusion Tensor Imaging (DTI)
  • Brain Perfusion compared with active placebo [ Time Frame: One week pre-treatment and one day post-treatment ]
    Arterial Spin Labeling (ASL)
  • Changes in sleep patterns [ Time Frame: From one week pre-treatment to two weeks post-treatment ]
    Actigraphy
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE LSD Therapy for Persons Suffering From Major Depression
Official Title  ICMJE LSD Therapy for Persons Suffering From Major Depression: A Randomised, Double-blind, Active-placebo Controlled Phase II Study
Brief Summary

Background: Major Depressive Disorder is one of the most prevalent mental illnesses, leading to substantial personal distress and economical consequences. Pharmacological Treatment is limited and relapse is frequent.

Lysergic acid diethylamide (LSD) was extensively investigated in humans in the 1950s and 1960s and was shown to attenuate depressive symptoms. Clinical research with LSD ended in the 1970s due to regulatory restrictions but its use for personal and recreational purposes continued. In recent years, there has been a renewed interest in the use of hallucinogens in psychiatric research and practices, reconsidering LSD's antidepressant potential. Larger, well-designed and placebo-controlled studies are warranted. This study will evaluate the potential benefits of LSD-assisted psychotherapy in patients suffering from Major Depressive Disorder.

Objective: To test the efficacy of LSD in patients with Major Depressive Disorder.

Design: Randomised, double-blind, active-placebo-controlled trial using 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.

Participants: 60 patients aged > 25 years with Major Depressive Disorder (according to DSM-V).

Main outcome measures: Change in depressive symptomatology (IDS-SR, BDI), anxiety (STAI), and general psychopathology (SCL-90) compared with active-placebo-assisted psychotherapy.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE Drug: LSD
LSD administration per os
Other Name: Lysergic Acid Diethylamide
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 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.
    Intervention: Drug: LSD
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 4, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
  • > 25 years
  • Sufficient understanding of the German language

Exclusion Criteria:

  • < 25 years
  • Concomitant diagnosis of past or present psychotic disorder
  • Concomitant diagnosis of past or present bipolar disorder
  • First degree relative with a psychotic disorder
  • Unable or unwilling to discontinue antidepressant medication
  • Pregnancy or breastfeeding
  • Known hypersensitivity to LSD
  • Somatic disorders including central nervous system (CNS) involvement
  • Known or suspected non-compliance, drug or alcohol abuse
  • Metal implants
  • Weight < 42 kg
  • Suicide risk or very likely to require psychiatric hospitalisation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Prof. Dr. med. Stefan Borgwardt, MD 061 325 51 11 ext +41 stefan.borgwardt@upkbs.ch
Contact: Prof. Dr. med. Matthias Liechti, MD 061 328 68 68 ext +41 matthias.liechti@usb.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03866252
Other Study ID Numbers  ICMJE BASEC 2018-02370
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
Investigators  ICMJE
Study Chair: Dr. med. Felix Müller, MD Department of Psychiatry
PRS Account University Hospital, Basel, Switzerland
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP